Katia Hala

Katia Hala
University of Pardubice

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117
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Introduction

Publications

Publications (117)
Article
Autoimmune diseases in human patients only become clinically manifest when the disease process has developed to a stage where functional compensation by the afflicted organ or system is not possible anymore. In order to understand the initial etiologic and pathogenic events that are generally not yet accessible in humans, appropriate animal models...
Article
Full-text available
The first standard nomenclature for the chicken (Gallus gallus) major histocompatibility (B) complex published in 1982 describing chicken major histocompatibility complex (MHC) variability is being revised to include subsequent findings. Considerable progress has been made in identifying the genes that define this polymorphic region. Allelic sequen...
Article
B(12) haplotype of the inbred chicken line CB (B12/B12) contains, like the bulk of chicken MHC(B) haplotypes, only a single dominantly expressed class I molecule (B-F). The peptide binding motifs for this major B-F12 molecule in chickens of Rous sarcoma regressor line CB (B12/B12) have been determined. Using stringent and relaxed motifs, several pe...
Article
Full-text available
The obese strain (OS) of chickens, which suffers from spontaneous autoimmune thyroiditis, is an excellent animal model for Hashimoto's thyroiditis and provides a unique opportunity to investigate the mechanisms underlying and driving the onset of the disease. Following recent advances in cloning chicken cytokines, we can now begin to investigate th...
Article
We analyzed the genetic regulation of spontaneous autoimmune thyroiditis (SAT) by means of crosses between Obese strain (OS) chickens with the disease, and healthy inbred chicken of line CB. Mononuclear cell infiltration of the thyroid was used as a criterion for the disease. We confirmed the existence of one recessive gene, regulating the suscepti...
Article
DNA vaccination is particularly efficient for induction of cytotoxic T-lymphocyte (CTL) response. In our experiments, we used MHC(B) congenic chicken lines CB and CC (regressors and progressors of v-src-induced tumours, respectively) and a mutated, non-oncogenic v-src gene construct as the DNA vaccine. A high degree of vaccine protection against on...
Article
Spontaneous autoimmune thyroiditis in obese strain (OS) chickens provides an excellent animal model for the study of Hashimoto's autoimmune thyroiditis in humans. The data presented in this paper indicate that nonspecific esterases (NSE) may play a role in or serve as a marker for the target organ susceptibility. Experiments have shown that follicu...
Article
Growth of tumors induced by Rous sarcoma virus (RSV) is controlled by alleles at the major histocompatibility complex locus in chickens, indicating that immunological host defense mechanisms play a major role. We show here that the resistance phenotype of CB regressor chickens can be partially reverted by treating the animals with a monoclonal anti...
Article
We have analyzed major histocompatibility complex (MHC) regulated immune response in congenic inbred chicken lines CB and CC, that differ from each other not only at the B haplotype but also in their ability to regress Rous sarcomas. The ratio of CD4+ to CD8+ peripheral blood lymphocytes is higher in CB chicken than in CC, as well as adherence pote...
Article
The influence of the chicken major histocompatibility (B) complex (MHC) on the adherence potential of monocyte-derived macrophages was examined using the congenic chicken lines CB and CC. These lines represent well-defined genetic models for the study of resistance (CB) or susceptibility (CC) to the progressive growth of Rous sarcomas. Using a mono...
Article
The involvement of CD4+ and CD8+ T cells in pathogenesis of spontaneous autoimmune thyroiditis (SAT) in obese strain (OS) chickens has not been studied in depth until now. We depleted CD4+ or CD8+ T cells in OS chickens by treatment with murine monoclonal anti-CD4 or anti-CD8 antibodies at 3 day intervals beginning at hatching. The birds were kille...
Article
Untreated control OS chickens develop spontaneous autoimmune thyroiditis (SAT). In contrast, OS chickens treated with a monoclonal anti-CD4 antibody failed to develop SAT. The preventive effect of anti-CD4 antibody on SAT was associated with the marked depletion of CD4+ T-cells by anti-CD4 treatment. These results indicate that CD4+ T-cells play a...
Article
The early, predictable, onset of spontaneous autoimmune thyroiditis (SAT) in Obese strain (OS) chickens provides a unique opportunity to analyse the mechanisms initiating autoimmunity which is virtually impossible to obtain in humans. In this study we focused on the respective roles of viruses and macrophages in the initiation of SAT. To analyse vi...
Article
Cornell K strain chickens received a diet supplemented with 0, 0.1 and 1.0 ppm T3 from the day of hatching. At 28 days of age, splenocyte suspensions were prepared and analyzed by flow cytometry for interleukin-2 receptor (IL-2R) and CD3 expression. The low T3 dose increased the percentage of resting small cells expressing IL-2R while the mean fluo...
Article
Full-text available
Skin grafts were performed to prove the level of genetic diversity in chicken populations of the Obese strain (OS), which develops a spontaneous Hashimoto's-like thyroiditis, and University of California at Davis (UCD) Line-200 chickens, which are hereditarily afflicted with progressive systemic sclerosis (scleroderma). As controls, Cornell C-strai...
Article
We studied T cell receptor variable beta (TCR V beta) gene usage by autoreactive T cells in spontaneous autoimmune thyroiditis (SAT) of obese strain (OS) chickens. Chicken alpha beta T cells may express either V beta 1 or V beta 2 genes, the products of which can be recognized by TCR2 and TCR3 monoclonal antibodies, respectively. Selective depletio...
Article
The oncogenic potential of different strains of Rous sarcoma virus (RSV) varies significantly in two Mhc(B) congenic chicken lines CB and CC and in their F1 hybrids with the unrelated inbred line IA. The Bryan high-titer pseudotype of RSV of antigenic subgroups D and B (BH-D, and BH-B) was highly oncogenic, eliciting mostly fatal, progressively gro...
Chapter
This chapter focuses on the obese strain (OS) of chickens with spontaneous autoimmune thyroiditis as a model for Hashimoto disease. The animal models that develop autoimmune diseases spontaneously parallel the human situation more closely. This is especially true for the OS chickens, which are afflicted with a spontaneously occurring hereditary aut...
Article
Considerable controversy exists concerning the role of aberrant MHC-class II antigen expression in the pathogenesis of organ-specific auto-immune disease. Since Obese strain (OS) chickens are afflicted with a spontaneously occurring autoimmune thyroiditis (SAT), we have readdressed this pivotal question by investigating the chronical appearance of...
Article
The growth pattern (progression/regression) of v-src DNA- and Rous sarcoma virus (RSV)-induced tumors was analogous on a panel of inbred chicken lines. The decisive role of the major histocompatibility complex [Mhc(B)] alleles in resistance to the progression of these tumors was formally proved in segregating backcross populations. The immune mecha...
Article
The aim of our experiments was the analysis of peripheral blood lymphocytes (PBL) and tumor infiltrating lymphocytes (TIL) in chicken inbred congenic lines, CB line with regressing and CC line with progressing RSV-induced sarcomas. For serological analysis, monoclonal antibodies to CD4, CD8, TCR1, TCR2, MHC class I and class II antigens were used....
Article
In both mammalian and avian systems, thymic nurse cells (TNC) have been shown to harbor a heterogeneous population of T lymphocytes (TNC-L) some of which exhibit a postselectional phenotype. By transplanting micromanipulated single chicken TNC onto the chorionallantoic membrane (CAM) of major histocompatibility complex (MHC)-disparate embryos, an e...
Article
Two closely related inbred lines of chickens, CB and CC, were compared for major histocompatibility complex (MHC) haplotype, response to tumors induced by Rous sarcoma virus and CD4:CD8 ratio. Genetic analysis showed that all the above traits were associated with the MHC. In all CB chickens, we found an additional endogenous virus, ev 17, a provira...
Article
In chickens from congenic inbred lines CB and CC that differ only in the major histocompatibility complex (MHC), we observed significantly different percentages of CD4+ and CD8+ cells in peripheral blood lymphocytes (PBL) and spleen. Positive cells were detected by indirect immunofluorescence test as analysed by flow cytometry. In both PBL and sple...
Article
F1-hybrids of Obese strain (OS) chickens, afflicted with spontaneous autoimmune thyroiditis (SAT), and normal, inbred CB chickens, do not develop severe thyroiditis. About 50% of these crosses show circulating autoantibodies to thyroglobulin (TgAAb), but the thyroid glands are only slightly infiltrated, suggesting that the target organ is not susce...
Article
The major histocompatibility complex (MHC) of chicken is the B complex, originally described as a blood group system. Its three classes of cell membrane antigens have been clearly defined by serological, histogenetic, biochemical, and molecular biological methods. Two of these classes are homologous to classes I and II of mammals (B-F and B-L respe...
Article
In the experiments to be described two congenic inbred lines CB and CC and two recombinant lines CB.R1 and CC.R1 were used. All four lines differ only in regard to the major histocompatibility complex (MHC). To determine the percentage distributions of the two cell subsets in peripheral blood lymphocytes (PBL) in these lines, monoclonal antibodies...
Article
Single chicken thymic nurse cells (TNC) placed onto the chorionallantoic membrane (CAM), showed that intra-TNC lymphocytes (TNC-L) possess a strong graft-versus-host reactivity (GVHR) in allogeneic MHC combinations. This reaction shows the morphological, phenotypic, and functional characteristics of a classical GVH reaction (GVHR). The induction of...
Article
A variety of immunological, endocrinological, and virological abnormalities have been implicated in the etiopathogenesis of spontaneous autoimmune thyroiditis (SAT) of Obese strain (OS) chickens, e.g., a general T cell hyperreactivity, an increased uptake of iodine into the thyroid gland, a diminution of the glucocorticoid tonus, and an OS-specific...
Article
Thymic nurse cells (TNC) are multicellular complexes composed of morphologically intact thymocytes internalized within epithelial cells. Due to their unusual features, they have been suspected to provide an appropriate microenvironment for T-cell repertoire acquisition. In recent functional studies in the chicken system, we have shown that intra-th...
Article
Thyroid glands of Obese Strain (OS) chickens become severely infiltrated by mononuclear cells and the occurrence of numerous germinal centers is a characteristic histological hallmark of the disease. Autoimmune thyroid destruction leads to thyroid hormone deficiency that entails the development of hypothyroid symptoms, such as small body size; mass...
Article
For the analysis of the genetic background of autoimmune thyroiditis we used the Obese strain (OS) chicken model which develops a SAT. Practically all animals from this strain show severe lymphoid infiltration of the thyroid gland and circulating autoantibodies against thyroglobulin (Tg-AAb) within a few weeks after hatching. Of the 3 MHC haplotype...
Article
In search for recombinants within the chicken major histocompatibility B complex, 1155 animals from crosses between the congenic lines CB (B12) and CC (B4) were tested with alloantibodies and monoclonal antibodies for the B-F (class I), B-L (class II), and B-G (class IV) antigens and by mixed lymphocyte reaction. The absence of detectable recombina...
Article
The Obese strain (OS) of chickens, which is afflicted with Hashimoto-like spontaneous autoimmune thyroiditis (SAT), displays elevated T cell proliferation, interleukin (IL) 2 production and IL2 receptor expression upon mitogen stimulation, and defects in the neuroendocrine control of the immune system including elevated corticos-teroid-binding glob...
Article
Analysis of the number of genes involved in the regulation of the expression of SAT in OS, by means of crosses with the unrelated inbred CB line, gave the following results: 1) The production of Tg-AAb is regulated by one or two genes; 2) the sensitivity of the thyroid to autoimmune attack is under the control of about 3 genes; 3) the expression of...
Article
It has been postulated that the establishment of acquired, neonatal immunologic tolerance is due to a "deficit" in interleukin 2 (IL-2). To test this hypothesis, chickens were made immunologically tolerant to both major and minor histocompatibility antigens by transplantation of skin grafts onto newly hatched recipients. In this study, we injected...
Article
In search for recombinants within the chicken major histocompatibility B complex, 1155 animals from crosses between the congenic lines CB (B12) and CC (B4) were tested with alloantibodies and monoclonal antibodies for the B-F (class I), B-L (class II), and B-G (class IV) antigens and by mixed lymphocyte reaction. The absence of detectable recombina...
Article
Monoclonal antibody INN-CH 16 recognizes a surface determinant exclusively present on activated chicken T lymphocytes. The present experiments suggest that this chicken activated T lymphocyte antigen (CATLA) represents the chicken IL-2 receptor or an associated structure, as (i) the kinetics of CATLA expression during T cell activation are analogou...
Article
Chickens of the Obese strain (OS) develop a hereditary spontaneous autoimmune thyroiditis (SAT) which closely resembles human Hashimoto's disease. Analysis of the endogenous viruses harboured by these animals revealed a new endogenous virus (ev22) detected as a 5.5kb Sac I fragment. Crossbreeding experiments showed thatev22 is vertically transmitte...
Article
Development of organ-specific autoimmune diseases depends on both an abnormal immune regulation and a genetically determined primary susceptibility of the target organ to the autoimmune attack. In addition to the essential genetically determined prerequisites there are also facultative, modulating factors that influence the outcome of an autoimmune...
Article
The enhanced T cell reactivity (ConA hyperresponsiveness and IL 2 hypersecretion) of spleen lymphocytes of Obese strain (OS) chickens with spontaneous autoimmune thyroiditis has recently been shown to be due to a defect in macrophage-derived non-specific suppressor factors that regulate IL 2 secretion and IL 2-promoted T lymphoblast proliferation i...
Article
Unlike many other tumors, experimentally induced Rous sarcomas in chickens have a definite tendency to regress spontaneously. Regression is under genetic control, but it is immunologically mediated although the target antigens that stimulate an immune response are unknown. Tumor cells in regressing sarcomas were found to express class II major hist...
Article
The expression of major histocompatibility complex (MHC) class I antigens in ontogenesis and the distribution of B-F+ cells, defined by means of a monoclonal antibody, were studied by indirect membrane immunofluorescence tests on suspensions of thymus, bursa, spleen, peripheral blood lymphocytes (PBL) and red blood cells (RBC) from 18-day-old chick...
Article
Immunologists working in the field of autoimmunity tend to concentrate all their efforts on the elucidation of possible malfunctions of the immune system, particularly pathologic changes of immune regulation. Also in the OS model various groups of investigators emphasized this approach, although it was already clear early in the history of this mod...
Chapter
Autoimmune diseases, both organ-specific and systemic, have a multifactorial basis with a definite genetic component. Most investigations on the theoretically and practically important problem of autoimmunity have focussed on the genetic basis of the aberrant immunological reactivity in experimental animals and man afflicted with autoimmune disease...
Article
A monoclonal antibody (INN-CH-16) was prepared which reacts with a cell surface antigen termed chicken activated T lymphocyte antigen. This antigen is expressed on antigen- or mitogen-activated T lymphocytes and is not present on nonstimulated lymphocytes. It has an apparent molecular mass of 48-50 kDa under reducing conditions. The value of this a...
Article
To determine the number and function of genes which are responsible for spontaneous autoimmune thyroiditis (SAT) in the obese strain (OS) of chickens we crossed birds of this strain (B15/B15) with those of the inbred CB line (B12/B12). The progeny was analyzed for autoantibodies to thyroglobulin (TgAAb) and for histopathological changes in the thyr...
Article
In this study we investigated the genetic background of primary abnormalities found in the thyroid gland of Obese strain (OS) chickens with spontaneous autoimmune thyroiditis (SAT), i.e., susceptibility to passively transferred antibodies to thyroglobulin (TgAb) and incomplete suppression of iodine uptake by thyroxine (T4). Several crosses between...
Article
Step-wise dilution of chicken thymus cell suspensions has been used to sequentially reveal suppressor, effector, and helper cells in these suspensions. The cells were tested either alone or in autologous mixture combinations with peripheral blood lymphocytes (PBL) as a source of effector cells. The assays studied were graft-vs-host reaction (GvHR)...
Article
Lymphomatous goiter (struma lymphomatosa) first described by Hashimoto in 19121, was shown to be an autoimmune disorder 30years ago2. In the sameyear an autoimmune thryoiditis was first induced experimentally by immunization with autologous thyroid extract and complete Freund's adjuvant3. Among the many insights gainedfrom the study of such experim...
Article
Lymphocytes were isolated from the infiltrated thyroid glands of 2- to 5-wk-old Obese strain (OS) chickens with spontaneous autoimmune thyroiditis (SAT). Immunofluorescence analysis performed by using a panel of monoclonal and polyclonal antibodies revealed that 60% of thyroid infiltrating leukocytes (TIL) were mature T cells, a large portion of wh...
Article
The B-L region of the chicken major histocompatibility complex (MHC), the so-called B-locus, corresponds to the murine H-2 I-region. Using alloantibodies and monoclonal antibodies to B-L we analyzed: (a) the tissue distribution of B-L+ cells, (b) the function of B-L+ cells, and (c) the possible role of B-L+ cells in the development of spontaneous a...
Article
Surface antigens on chicken thymus and bursa cells were analyzed by immunoprecipitation using polyclonal and monoclonal antisera raised against (and specific for) thymus (ATS) or bursa (ABS) cells, respectively. The antigens identified were compared with those governed by the B-F, B-L and B-G regions of the chicken major histocompatibility complex...
Article
The functional of B-L (Ia-equivalent)-positive (B-L+) adn -negative (B-L-) chicken peripheral blood lymphocytes (PBL) was studied in vitro and in vivo. The PBL were first stained in direct immunofluorescence tests with a fluorescein isothiocyanate-labelled anti-B-L alloantiserum and then separated by means of a fluorescence-activated cell sorter. I...
Article
Chicken thymic nurse cells (TNC) were isolated and their plasma membrane antigens were characterized by immunofluorescence with a panel of allo-, hetero-, and monoclonal antibodies. Analogous to the murine system, chicken TNC are localized in the subcapsular region of the cortex and were strongly B-L and B-F positive (MHC Ia and H-2 D, K equivalent...
Article
Using an indirect hemagglutination assay we tested sera from 94 healthy normal White Leghorn (NWL) and 117 Obese strain (OS) chickens with spontaneous autoimmune thyroiditis for the presence of "natural" antibodies against major histocompatibility complex (MHC) antigens expressed on red blood cells (RBC). In both groups older animals had a signific...
Article
Specific antisera reacting with B-L (Ia-like) antigens were prepared by reciprocal immunization of animals from the congeneic lines CB and CC. The resulting antisera were tested either in direct or indirect immunofluorescence tests and stained 10-16% of peripheral blood cells (PBL). Of the B-L+ cells, 90% were B cells and 8% were T cells. After in...
Article
The major histocompatibility complex (MHC) of Gallus gallus is the B complex of which three classes of cell-membrane antigens have been clearly defined by serological, histogenetic, and biochemical methods. Two of these classes are homologous to classes I and II of mammals (B-F and B-L, respectively), while the third (B-G) is a differentiation anti...
Article
Chickens of the Obese strain (OS) develop a spontaneous, hereditary autoimmune thyroiditis during the first weeks of life which parallels human Hashimoto's thyroiditis in all clinical, histopathological and serological aspects. This review summarizes the results from investigations on this strain with special emphasis on the pathogenic effector mec...
Article
The chicken MHC (B complex) initially described by Briles as controlling blood antigens, is now known to be composed of at least three regions, L, F and G. Two of these, F and G, were described on the basis of recombinants found in a study of over 10,000 chickens. On the basis of biochemical, tissue distribution and functional analyses, F correspon...
Article
In the chicken MHC there exist two regions, designated F and G, which were separated by crossing-over. The F region contains genes controlling all functions characteristic of the MHC. So far only one gene has been assigned to the G region and it is responsible for the presence of an RBC antigen. When cross immunizing animals of the congenic lines C...
Article
The Obese strain (OS) of chickens was developed about 15 years ago by selective breeding for the phenotypic trait of hypothyroidism [1, 2]. The fact that the clinical symptoms are attributable to a spontaneously arising thyroiditis which is autoimmune in nature was first recognized 5 years later [3]. In subsequent years this avian model was establi...
Article
Two loci of the chicken MHC (the B complex) are expressed in erythrocytes, B-F and B-G. The former is homologous to the murine K and D loci and is also expressed in all white blood cells, while the latter is apparently restricted to RBC and is of unknown relationship to H-2 and HLA loci. A recombinant between two congenic, MHC-different strains, CB...
Article
F1 chicken hybrids of the inbred lines CC and IC were given injections of erythrocytes from CB line chickens (differing at alloantigens of the major histocompatibility system B) or IA line chickens (differing at the A blood group system alloantigens). Injected erythrocytes were labelled with 51Cr and their gradual elimination from the recipient's c...
Article
Comparison of two inbred chicken lines (Fx > 99.9%) revealed significant differences in shape of the red blood cells (RBC). The length-width index was lower for both sexes in IC-line (1.46) when compared to CB-line chickens (1.88). Phenotypic expression of this character in F1 hybrids and both backcross groups corresponded to the common manifestati...
Article
Among hybrids of the inbred chicken lines, cock 1357 was found to be chimaeric in red blood cells. This cock possessed three serologically distinct types of erythrocytes and two types different in shape and size.
Article
In the course of study of alloantigenic immunoglobulin polymorphisms in 10 inbred chicken lines we detected 7 IgG allotypic specificities and 3 IgM allotypes. All birds in a given line possessed a unique combination of several IgG alloantigenic specificities (forming the phenogroup) which is presumably controlled by one allele at the locus designat...
Article
Among hybrids of the inbred lines, a chicken was found to be chimaeric in red blood cells and skin cells and to produce 3 types of sperm cells. This bird could have originated either from the fusion of 2 blastoderms or from the fertilization and fusion of the oocyte and the 2nd polar body.
Article
The activity of complements from various sources was compared in the complement-mediated cytotoxicity test, using chicken alloantisera. The highest cytotoxicity index was obtained with a pool of complements from fresh guinea pig serum and chicken serum. No difference in activity between complements from chickens of the different inbred lines was fo...
Article
Tolerance to alloantigens of the A and B systems in chickens has been induced by multiple injections of RBC and tested by the elimination of 51Cr-labelled RBC of the same specificity. Three doses consisting of at least 108 RBC each in the B system and 107 RBC in the A system were needed to induce tolerance in newly hatched chicks. Futhermore, it wa...
Article
In a population of (CB X CC)F1 X WB hybrids, a chicken was found with a presumably recombinant haplotype, BR1, whose antigenic products detectable by hemagglutination contained determinants derived from both parental haplotypes, i.e. B1 (from CB) and B2 (from CC). This recombinant bird and its progeny from different crosses were tested by skin graf...