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ABSTRACT: Proliferative response of splenic T cells of C57BL/6 mice to mutant major histocompatibility complex (MHC) class I antigen (H-2Kbm1) was examined with regard to the role of accessory cells. T cell proliferation in mixed lymphocyte culture (MLC) was not induced when accessory cells were removed from stimulator spleen cells by passage through Sephadex G-10 or nylon-wool column. Anti-Iab antibodies did not inhibit the proliferative response to class I antigen, whereas the same antibodies completely blocked the response to class II antigen (Iabm12). Accessory cells may not be mere presenters of MHC class I antigen because stimulator cells fixed with 0.05% paraformaldehyde lost the stimulating function. The proliferative response was partially recovered by the addition of recombinant interleukin 1 (IL-1) and/or IL-2 to MLC devoid of stimulator type accessory cells. It is concluded that stimulatory type accessory cells were obligatorily involved in the T cell proliferation, and the production of IL-1 by accessory cells is thought to play a critical role in this process
Scandinavian Journal of Immunology 06/2006; 27(3):311 - 318. · 2.23 Impact Factor
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ABSTRACT: Mechanisms of the activation of T cells responding to major histocompatibility complex (MHC) class I antigen were investigated with special reference lo interleukin 1 (IL-1) production from stimulator-type accessory cells. For this purpose, we used mainly fractionated Lyt-2+ T cells of C57BL/6 (B6) mice as responder cells and irradiated spleen cells or those deprived of adherent cells of B6. C-H-2bm1 (bm 1) mice as stimulator ceils. Lyt-2+ T cells of B6 mice proliferated in the presence of irradiated whole spleen cells of bm1 mice but did not to Sephadex G-10 column-passed bm1 spleen cells. The unresponsiveness in the latter case was overcome by the supplement of recombinant IL-1 and/or IL-2 in the culture medium. These interleukins were shown to promote the proliferative response of B6 Lyt-2+ T cells in the presence of stimulator-type for B cells. Both interleukins also facilitated the generation of cytotoxic T cells from BA Lyt-2+ cells to H-2Kbm1 antigen in the mixed lymphocyte culture deficient in stimulator-type accessory cells. IL-1 was shown to enhance the expression of IL-2 receptor on the responding Lyt-2+ T cells as assessed by flow cytometry. IL-1 binding to responding T cells were also assayed by means of iodinated IL-1 and was shown to increase significantly on responding Lyt-2+ cells. Overall results indicate that accessory cells might play dual roles in the activation of Lyt-2+ T cells responding to allogeneic MHC class 1 antigen: direct presentation of the antigen to responder T cells and production of IL-1. Both signals are essentially required for Lyt-2+ T cells responding to allogeneic MHC class I antigen to initiate proliferation and also to differentiate into cytotoxic T cells.
Scandinavian Journal of Immunology 06/2006; 29(3):343 - 351. · 2.23 Impact Factor
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ABSTRACT: In this paper, we examined the induction of autoimmune-like histologic changes in the liver and other organs of mice undergoing graft-versus-host reaction (GVHR) with MHC class I disparity by the administration of bacterial lipopolysaccharide (LPS), on the assumption that stimulation with LPS could be an exacerbating factor. Spleen cells of C57BL/6 (B6) mice were injected twice into (B6 x bml) F1 recipient mice at an interval of 7 days to induce MHC class I GVHR and then challenged with 1 microg of LPS intravenously on the next day of the cell transfer. The hepatic lesions of the group of MHC class I GVHR mice challenged with LPS showed marked cellular infiltration at the portal area and focal necrosis was observed in the hepatic lobule. The major infiltrating cells were CD8+, and others including CD4+ cells being of minor populations. In addition, ductal lesions in extrahepatic organs, including the pancreas and salivary glands also showed marked cellular infiltration. Thus, we have demonstrated that LPS induced ductal lesions in mice with MHC class I disparity. CD8+ cells were detected at the destructive hepatic lesions, which might be effector cells. These findings indicate that LPS might be one of the potential factors which augment autoimmune-like lesions.
Immunology Letters 01/1998; 59(3):159-70. · 2.53 Impact Factor
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K Suzuki,
T Narita,
R Yui,
K Ohtsuka,
S Inada,
T Kimura,
Y Okada,
M Makino,
T Mizuochi,
H Asakura, M Fujiwara
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ABSTRACT: Murine leukemia virus, LP-BM5, induces severe immunodeficiency with abnormal lymphoproliferation in susceptible C57BL/6 mice. In a previous study, it was shown that a Sjögren's syndrome-like systemic exocrinopathy is induced in the virus infected mice.
To examine lymphocyte functions of the virus infected mice.
Four-week old mice were inoculated with the virus and their spleen cells were transferred into syngeneic nu/nu mice. Their organs were examined by light and electron microscopy. Phenotypes of the colon infiltrating cells were examined by flow cytometry.
All nu/nu recipients had died by six weeks after cell transfer, showing runting disease like cachexia with diarrhoea and anal bleeding. Histopathological examination revealed that systemic exocrinopathy was adoptively transferable and that the colon became thickened due to mononuclear cell infiltration into the mucosal and submucosal layer with hyperplasia of intestinal epithelial cells. No virus particles were found in the colon. Flow cytometric analyses revealed that most of the infiltrating CD4+ T cells showed CD45RBlow. No intestinal lesions were observed in the virus infected mice nor in nu/nu mice inoculated with normal lymphocytes.
Lymphocytes of the virus infected mice induced colitis and hyperplasia of intestinal epithelial cells as well as systemic exocrinopathy in nu/nu mice. Our experimental system may give some insight into intestinal lesions associated with virus infection.
Gut 09/1997; 41(2):221-8. · 10.11 Impact Factor
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ABSTRACT: Interaction between intercellular adhesion molecule 1 (ICAM-1) and lymphocyte function-associated antigen 1 (LFA-1) might be involved in the pathogenesis of liver diseases. We investigated whether monoclonal antibodies (mAbs) against these two adhesion molecules could inhibit the formation of primary biliary cirrhosis (PBC)-like lesions in an animal model using graft-versus-host reaction (GVHR) with major histocompatibility complex class II disparity. PBC-like hepatic lesions such as cellular infiltration of portal area and nonsupprative destructive cholangitis (NSDC) were generated by injecting spleen T cells of C57BL/6 (B6) mice into (B6. C-H-2bm12 X B6) F1 mice. In the liver of these mice, increased number of LFA-1-positive cells and enhanced expression of ICAM-1 on sinusoidal endothelial cells and bile duct epithelial cells were observed immunohistochemically, when compared with F1 mice without GVHR. Hepatic lesions of these mAb-treated mice were almost completely inhibited in these mice compared with GVHR mice. Furthermore, we studied to determine which anti-LFA-1 mAb or anti-ICAM-1 mAb was essential to inhibit the hepatic lesions. Mice solely treated with anti-LFA-1 mAb showed significant inhibition of hepatic lesions, whereas treatment with anti-ICAM-1 mAb could not inhibit the lesions. Despite the inhibition of hepatic lesions, induction of GVHR and production of antimitochondrial antibodies were not impaired in mAb-treated mice. We conclude that LFA-1 mediates cell infiltration into the liver in this murine model of GVHR and suggest a possible therapeutic role of mAbs to this adhesion molecule in selective autoimmune liver diseases.
Hepatology 11/1996; 24(4):888-94. · 11.66 Impact Factor
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ABSTRACT: C57BL/KsJ mice carrying homozygous db/db mutation (db/db mice) are characterized by extreme obesity and early onset of hyperglycemia. In an attempt to rectify diabetes of these mice, a pancreatic beta cell line MIN6, which retains glucose-inducible insulin secretion, was transplanted subcutaneously into the back of the mice. Glucose and insulin levels of individual mice were examined biweekly and their weight gain weekly. All mice were sacrificed at 100 days after the transplantation of MIN6 cells. In db/db mice that had received MIN6 cells, blood insulin levels were restored and blood glucose levels were reduced to those of non-diabetic mice, although they remained obese. Glucose tolerance test suggested that transplanted MIN6 cells responded to loaded glucose as beta cells of non-diabetic mice. Immunohistochemical study showed that transplanted MIN6 cells produced insulin. Fatty liver associated with diabetes mellitus observed in db/db mice was not found in the MIN6 cell-transplanted mice. Implication of the results is discussed with reference to potential therapies for severe diabetes.
Diabetes Research and Clinical Practice 06/1996; 32(3):125-33. · 2.75 Impact Factor
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ABSTRACT: We report in this paper on obvious fibrotic lesions in the liver of mice undergoing specified graft-versus-host reaction (GVHR). B6 CD8+ splenocytes were transferred into (bm 12 x bm 1)F1 mice to induce GVHR. Recipient mice had been thymectomized and administrated with anti-CD8 monoclonal antibody (mAb) to deplete CD8+ cells from the hosts. Two weeks after the mAb administration, recipient mice were injected with B6 CD8+ cells and sacrificed further two or four weeks later for analyzing hepatic lesions histopathologically. Light microscopic analyses revealed the presence of concentric fibrosis around both small and large duct levels and the infiltration of mononuclear cells into portal areas. Focal necrosis of hepatocytes was also detected electron-microscopically. These findings suggest that CD8+ T lymphocytes might play an important role in the induction of fibrotic lesions in the liver.
Autoimmunity 02/1995; 22(3):163-71. · 2.47 Impact Factor
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ABSTRACT: Autoimmune-like hepatic lesions were induced by injection of CD4+ T cells from B10.Thy-1.1 mice into MHC class II-disparate (B10.Thy-1.1 x bm12)F1 mice. Hepatic lesions characterized by mononuclear cell accumulation in the portal area of the central vein and around interlobular bile ducts were observed in these recipients. The morphologic features of the lesions resembled primary biliary cirrhosis. The origin of T cells invading at the site of the hepatic lesions was immunohistochemically analyzed. It was shown that many recipient-derived T cells were present at the lesions and that some of them infiltrated the bile duct epithelia. Furthermore, the lesions were weakened when recipient-type T cells were depleted by thymectomy and the administration of anti-Thy-1.2 monoclonal antibody. Recipient-derived T cells were observed to take part in the formation of autoimmune hepatic lesions. These findings suggest the possibility that the tolerance of self-reactive T cells is abrogated by the graft-versus-host reaction.
Autoimmunity 02/1995; 20(2):121-7. · 2.47 Impact Factor
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ABSTRACT: Chronic graft-versus-host disease (GVHD) following bone marrow transplantation often gives rise to a severe autoimmune-like state. To investigate the immunopathogenesis of this diseased state, mice receiving a transplant of lymphocytes with major histocompatibility complex (MHC) class II disparity (the simplest model of chronic GVHD) were examined. (B10.Thy-1.1 x B6.C-H-2bm12) F1 mice were injected with parental B10.Thy-1.1 CD4+ splenic T cells. These mice showed intensive lymphocyte infiltration of the target organs, including the liver, salivary glands and pancreas. Indeed, the cell numbers yielded from the spleen and liver were increased, and polyclonal B-cell activation was induced by 14 days after injection. More strikingly, more than 80% of such expanding lymphocytes in the target organs became T cells with T-cell receptors (TCR) of intermediate intensity (i.e. intermediate TCR cells) that carried the properties of extrathymic origin. Despite the homogeneous expansion of intermediate TCR cells in GVHD mice, these T cells were polyclonal in terms of V beta usage. These results, in conjunction with the data using the thymectomized mice as recipients, suggested that extrathymic, intermediate TCR cells possibly of recipient origin might be intimately related to the pathogenesis of the autoimmune-like state resulting from chronic GVHD.
Immunology 11/1994; 83(2):205-12. · 3.32 Impact Factor
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ABSTRACT: We previously reported that primary biliary cirrhosis (PBC)-like hepatic lesions were induced in (bm12xB6)F1 mice undergoing graft-versus-host reaction with major histocompatibility complex class II disparity. In this paper, we report on a new experimental system, enabling establishment of more progressed stages of PBC-like lesions and clarification of the role of CD8+ cells in the development of the lesions.
Recipient (bm12xbm1)F1 mice were thymectomized and administered anti-Lyt-2 monoclonal antibodies intraperitoneally to deplete host CD8+ cells as completely as possible. The treatment was necessary to induce autoimmune hepatic lesions in this type of F1 mice. Recipients were divided into five groups: group 1 received B6 CD4+ cells on day 0 and 2 weeks later, B6 CD8+ cells; group 2, only B6 CD4+ cells on day 0; group 3, only B6 CD8+ cells on day 14; group 4, B6 CD4+ on day 0 plus F1 CD8+ cells 14 days later. Cell transfer was not done in group 5. All of the mice were killed on day 28 for examination by light and electron microscopy and also by immunohistochemistry.
PBC-like hepatic lesions without tissue destruction were induced in the mice of group 2, as was previously reported. In addition to similar lesions to group 2, destruction of hepatocytes and bile duct epithelia was induced in the mice of group 1. Weak lymphocytic infiltration and periductal concentric fibrosis were observed in the mice of group 3. PBC-like hepatic lesions without tissue destruction were induced in mice of group 4 as were those of group 2. However, the cellular infiltration was much weaker.
For the animal model of PBC, we have devised a new experimental system in which the role of donor or host type CD8+ cells is assessable. Tissue-destructive lesions were induced only in mice that received donor CD4+ cells followed by CD8+ cells. The PBC-like lesions were suppressed by host type CD8+ cells. These results suggest that destructive hepatic lesions of PBC might progress through CD8+ cells in cooperation with CD4+ cells, and that host type CD8+ cells could act as "regulatory" T cells for the progression of the lesions.
Laboratory Investigation 06/1994; 70(5):609-19. · 3.64 Impact Factor
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ABSTRACT: Inbred strains of mice differ markedly in their relative susceptibility to the development of lymphoproliferation and immunodeficiency, a syndrome termed mouse AIDS (MAIDS), after infection with the LP-BM5 mixture of murine leukemia viruses (MuLV). The etiologic virus in this mixture is replication defective (BM5def) and encodes only a variant gag protein. Genetic determinants of resistance and susceptibility to induction of MAIDS reside both within and outside the MHC. In strains with C57BL background genes, the MHC haplotypes associated with resistance to disease include d and a, whereas haplotypes b, s, and q are associated with sensitivity. Previous studies showed that MHC class I genes (H-2Dd, H-2Ld) mapping in the D end of H-2 and other genes mapping proximal to the D end determine resistance to MAIDS. This paper examines the nature of these non-D end MHC genes using assays of MHC recombinant and transgenic mice. We demonstrate that expression of E alpha d confers significant resistance to MAIDS, even in mice that do not express H-2Dd/H-2Ld. Unexpectedly, we found that E alpha polymorphisms can significantly influence resistance, with H-2b mice bearing E alpha d as a transgene having greater resistance to MAIDS than mice bearing an E alpha k transgene. E alpha d-mediated resistance to MAIDS was associated with decreased levels of the BM5def genome in splenic DNA, suggesting that E alpha genes exert their effect by enhancing antiviral activity.
The Journal of Immunology 05/1994; 152(8):4157-64. · 5.79 Impact Factor
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ABSTRACT: Sjögren's syndrome (SS) is characterized by lymphocytic infiltration into, and destruction of exocrine glands, resulting in dryness of the mouth and eyes. The disease is considered to have an autoimmune etiology, however, its etiopathogenesis remains largely unknown. Recently, retrovirus is suggested to participate in the pathogenesis of SS, because SS-like lesions are reported in HIV infection or in human T cell leukemia virus type I infection. Moreover, human intracisternal A-type retroviral particles are reported to be detected in SS patients. During the course of our study on the histopathology of mice infected with a murine retrovirus, we happened to find SS-like exocrinopathy in those mice.
Four-week-old C57BL/6 (B6) mice were injected intraperitoneally with LP-BM5 murine leukemia virus. This virus is known to induce splenomegaly, lymphadenopathy followed by lymphoid malignancy, and profound immunodeficiency in sensitive strains of mice. From 4 to 16 weeks after the virus inoculation, the infected mice were sacrificed and their submandibular and lacrimal glands were analyzed light and electron microscopically and immunohistochemically. The existence of the virus in the lesion in situ was also analyzed by the same method, and additionally by a polymerase chain reaction method.
Periductal lymphocytic infiltration into the submandibular and lacrimal glands was observed in all the virus-infected mice at 4 weeks after the infection and progressed with time. Extraglandular lymphocytic infiltration was also observed in liver, kidney, lung, and pancreas. Immunohistochemical examination revealed that most infiltrating cells into the glands were composed of CD3+ T cells (CD4-dominant), Mac-1+ cells, and B220+ cells. The virus genome was detected in submandibular glands by immunohistochemistry or by polymerase chain reaction. In addition, retroviral particles were secreted into the lumen of exocrine ducts of submandibular glands.
This might be an SS animal model that is induced by a certain defined retrovirus. This experimental system might provide us with valuable information for analyzing the mechanisms of how a retrovirus could induce SS.
Laboratory Investigation 11/1993; 69(4):430-5. · 3.64 Impact Factor
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ABSTRACT: The fate of cultured keratinocyte (KC) allografts remains controversial. Although prolonged survival of cultured KC allografts in naive mice has been reported, the detailed mechanisms remain undetermined. Furthermore, it was also reported that in the human cultured KC allografts do not survive permanently, and they are rapidly replaced by recipient cells. In the present study, we have addressed this issue and obtained findings that cultured KC allografts survive for a prolonged period in naive mice under the conditions in which reepithelization by recipient cells is prevented. However, the same cultured KC allografts were rejected when they were grafted onto recipients primed with allogeneic spleen cells or full-thickness skin grafts. To clarify the mechanisms behind these findings, the allostimulatory ability of cultured KC and their susceptibility to alloreactive cytotoxic T cells were examined in vitro. In a mixed epidermal cell-lymphocyte reaction, cultured KC were unable to induce allospecific proliferative responses of naive T cells. On the other hand, primed T cells from presensitized mice showed weak but significant proliferative responses against allogeneic KC. It also was confirmed that cultured KC are susceptible to lysis by alloreactive cytotoxic T cells. These data indicate that prolonged survival of cultured KC allografts in naive mice is attributable to a defect in the afferent, but not the efferent, phase of the rejection process that is caused by the weak allostimulatory ability of cultured KC. This assumption was also supported by the finding that spleen cells from the recipient mice bearing long-surviving KC allografts retain in vitro responsiveness against stimulator cells syngeneic to the grafted KC. Taken together, these findings indicate that long-term survival of cultured KC allografts in naive mice may be due solely to the weak allostimulatory ability of cultured KC, but not to loss of susceptibility to alloreactive cytotoxic T cells after culture of KC or induction of tolerance in the recipient mice bearing KC allografts.
Transplantation 09/1993; 56(2):265-9. · 4.00 Impact Factor
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ABSTRACT: Staphylococcal enterotoxins (SEs) can bind major histocompatibility antigens and stimulate T cells which bear particular types of T cell receptor. Therefore, it has been postulated that SEs may trigger or modulate the development of autoimmune diseases caused by T cells. In the present study, we examined the effects of SEs on rat encephalitogenic T cells and the clinical manifestation of experimental autoimmune encephalomyelitis (EAE). SED, but not other SEs, stimulated encephalitogenic T cells. Furthermore, culture of lymphoid cells from myelin basic protein (MBP)-immunized rats with SED augmented the clinical manifestation of passively transferred EAE, whereas SEA and SEB showed no significant EAE-transfer ability. Flow cytometric analysis demonstrated that in vitro SED stimulation of T cells from MBP-immunized rats, but not from normal rats, resulted in selective expansion of V beta 8.2+ T cells. Consistent with in vitro findings, in vivo administration of SED modulated EAE elicited by immunization with MBP. SED given after the immunization augmented clinical manifestation, especially at low doses. On the other hand, SED given 7 days before the immunization suppressed the development of EAE in a dose-dependent manner. Interestingly, the same toxin given at a dose of 20 micrograms to thymectomized rats induced enhanced EAE regardless of the timing of administration. It has already been established that SEs stimulate T cells bearing a particular type of TCR V beta chain and subsequently induce unresponsiveness of these T cells. The present results suggest that a similar mechanism may operate in rats after the toxin treatment and MBP immunization. However, in vitro assay showed that the proliferative responses of T cells from EAE-suppressed rats to MBP and SED were not eliminated, suggesting that SED-induced suppressor T cells may also play some roles in EAE suppression. The present study has shown that SED, one of the superantigens, modulates an autoimmune disease. More importantly, its effects are not uniform, but instead are closely related to the dose of the toxin, timing of toxin exposure, and the status of hosts.
Cellular Immunology 08/1993; 149(2):268-78. · 1.97 Impact Factor
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ABSTRACT: Immunohistochemical examination demonstrated expression of intercellular adhesion molecule-1 (ICAM-1) on 17 of 44 transitional cell cancers (TCCs) but not on normal transitional cells. ICAM-1 was frequently expressed in higher stage tumors, especially in those with abundant immune cells scattered within tumor. Analysis of infiltrating immune cells showed that they were composed mainly of T lymphocytes and a smaller number of macrophages bearing the lymphocyte function-associated antigen-1 (LFA-1). Expression of ICAM-1 on transitional cell cancer cell lines was augmented by in vitro treatment with interferon-gamma, tumor necrosis factor-alpha, and interleukin-1 beta. Furthermore, Northern blot analysis revealed higher quantities of a 3.3-kb RNA in T24 cells exposed to interferon-gamma or tumor necrosis factor-alpha. These results suggest that the expression of ICAM-1 on transitional cell cancers might be modified by cytokines produced by infiltrating immune cells, which might facilitate immune responses against cancer cells.
American Journal Of Pathology 08/1993; 143(1):191-8. · 4.89 Impact Factor
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ABSTRACT: In a previous report, we showed that the injection of parental CD4+ T cells into major histocompatibility complex (MHC) class II disparate F1 hybrid mice induces autoimmune-like graft versus-host reaction (GVHR) resembling systemic lupus erythematosus (SLE) and the hepatic lesion of primary biliary cirrhosis (PBC). In the present study, we examined whether or not simultaneous or subsequent injection of CD8+ T cells changes the GVHR form. When parental CD8+ T cells together with CD4+ T cells were injected into MHC class I plus class II-disparate F1 mice, autoimmune phenomena did not develop and alternatively a profound immunosuppressive state was induced. Furthermore, ongoing autoimmune-like GVHR induced by CD4+ T cells was also suppressed by later injection of CD8+ T cells. In these mice, an increase of donor type CD8+ T cells and a marked decrease of host B and T cells in the spleen were observed. The spleen cells from these mice strongly inhibited the mitogenic response of normal spleen cells against lipopolysaccharide (LPS). In vitro studies demonstrated that this immunosuppression was not induced by CD8+ T cells themselves but by macrophages which produced suppressive factor(s) by LPS stimulation. These findings were discussed with reference to suppressive mechanisms of GVHR.
Immunology 06/1993; 79(1):95-102. · 3.32 Impact Factor
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ABSTRACT: Expression of intercellular adhesion molecule-1 (ICAM-1) and major histocompatibility complex (MHC) antigens, and characterization of tumor-infiltrating mononuclear cells (TIM) were examined immunohistologically in 10 specimens of seminoma. ICAM-1 and MHC antigens were not detected on normal spermatogenic cells. ICAM-1 and MHC class I antigens were variably expressed in 7 and 9 seminomas, respectively, whereas class II antigens were not detected. Although the degree of expression of ICAM-1 and MHC antigens was not correlated with any clinical or histopathological factors, neither of the antigens was detected on an anaplastic seminoma. Various numbers of TIM were detected in all of the seminoma, and comprised mainly T cells bearing the lymphocyte function-associated antigen (LFA)-1. No significant correlation was noticed between the degree of lymphocyte infiltration and ICAM-1 or MHC antigen expression. Although ICAM-1 and MHC class I antigens were expressed in seminoma, possibly facilitating an anti-tumor reaction of host, their expression remained low in several cases, despite marked lymphocyte infiltration within the tumor.
The Journal of Urology 04/1993; 149(3):659-63. · 3.75 Impact Factor
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ABSTRACT: Infection with the avirulent Fukaya strain of Toxoplasma gondii induced few inflammatory responses in the brain of C57BL/6 mice. When mice with chronic infection with the Fukaya strain were challenged with murine leukemia virus (MuLV) LP-BM5, which is known to induce a remarkable immunodeficiency in mice, those mice suffered from a severe encephalitis. Infiltration of mononuclear cells was remarkable in both meninges and parenchyma in those mice. Numerous sites of acute focal inflammation were noted in the brain and the presence of tachyzoites and Toxoplasma antigens was demonstrable in those areas by immunoperoxidase staining using rabbit anti-Toxoplasma IgG antibodies. All mice infected with both T. gondii and LP-BM5 MuLV died from 9 to 14 weeks after the virus infection, whereas no mice died in the infection with either T. gondii or the virus alone. Spleen cells from the mice with coinfection failed to respond to both T cell (Con A) and B cell mitogens (LPS) in vitro in contrast to the cells from mice infected with T. gondii alone that responded to those mitogens just as cells from normal mice did. Mice chronically infected with T. gondii and challenged with LP-BM5 MuLV appears to provide a good animal model of toxoplasmic encephalitis which is a major cause of morbidity and mortality in AIDS patients.
Experimental Parasitology 03/1993; 76(1):39-45. · 2.12 Impact Factor
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ABSTRACT: Splenic CD8+ (Lyt-2+) cells of C57BL/6 mice were injected into semiallogeneic (NZB x BXSB)F1 mice, which spontaneously develop lupus nephritis, in order to examine whether the disease was somehow modified by the occurrence of graft-versus-host reaction. The development of lupus nephritis in the F1 recipients was strongly inhibited and immunopathological parameters such as anti-DNA antibodies, circulating immune complexes (CIC) and splenic immunoglobulin-producing cells (IgPC) were markedly reduced. The injection of CD4+ (L3T4+) T cells into F1 recipients did not result in similar effects. These findings suggest that the development of autoimmune disease could be ameliorated by CD8+ cells responding to MHC class I antigens. The significance of the data is discussed in terms of the treatment of autoimmune diseases.
Clinical & Experimental Immunology 12/1992; 90(2):260-5. · 3.36 Impact Factor
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ABSTRACT: The antigen-presenting capability of various types of brain cell, such as primary mixed glial cells, astrocytes and microglia, was examined under conditions in which Ia antigen expression on the cultured cells mimicked that in the central nervous system (CNS) of rats with experimental autoimmune encephalomyelitis (EAE). In the CNS of rats with EAE, microglia but not astrocytes express Ia antigens. To produce such conditions, cultured brain cells were treated with various concentrations of interferon-gamma (IFN-gamma). It was revealed that in vivo-like conditions were produced when cultured brain cells were treated with less than 100 U/ml IFN-gamma. Under such conditions, microglia presented an antigen, myelin basic protein (MBP), to MBP-specific T-cell lines. Astrocytes, on the other hand, did not show antigen-presenting ability, but rather suppressed T-cell proliferation. Primary mixed glial cells, mainly comprising astrocytes and microglia, were also weak antigen-presenting cells (APC). These findings suggest that brain cells comprising various types of cell with regard to APC function do not up-regulate the proliferation of encephalitogenic T cells in vivo, although a particular type of brain cell, i.e. microglia, show antigen-presenting capability.
Immunology 07/1992; 76(2):209-16. · 3.32 Impact Factor
