Abigail C Buenafe

Portland VA Medical Center, Portland, Oregon, United States

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Publications (46)179.17 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Treatment with partial (p)MHC class II-β1α1 constructs (also referred to as recombinant T-cell receptor ligands - RTL) linked to antigenic peptides can induce T-cell tolerance, inhibit recruitment of inflammatory cells and reverse autoimmune diseases. Here we demonstrate a novel regulatory pathway that involves RTL binding to CD11b(+) mononuclear cells through a receptor comprised of MHC class II invariant chain (CD74), cell-surface histones and MHC class II itself for treatment of experimental autoimmune encephalomyelitis (EAE). Binding of RTL constructs with CD74 involved a previously unrecognized MHC class II-α1/CD74 interaction that inhibited CD74 expression, blocked activity of its ligand, macrophage migration inhibitory factor, and reduced EAE severity. These findings implicate binding of RTL constructs to CD74 as a key step in both antigen-driven and bystander T-cell tolerance important in treatment of inflammatory diseases.
    Journal of Autoimmunity 09/2012; 40(1). DOI:10.1016/j.jaut.2012.08.004 · 8.41 Impact Factor
  • M. Huckans · A. Buenafe · J. Huan · A.A. Vandenbark · J.M. Loftis ·
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    ABSTRACT: Approximately half of methamphetamine dependent adults experience mood, anxiety, and other psychiatric disorders up to three years or longer into remission. These neuropsychiatric impairments contribute to relapse and poor treatment retention. However, the molecular mechanisms responsible for the persistence of neuropsychiatric impairments are poorly defined. We investigated the effects of methamphetamine dependence on immune cell function as measured by in vitro reactivity to neuroantigens and evaluated the relationship between methamphetamine-induced neuropsychiatric impairment and altered peripheral immunoreactivity. Seventy-three research participants (42 adults in recovery from methamphetamine dependence; 31 non-dependent controls) completed neuropsychiatric measures and a blood draw. Mononuclear cells were stimulated with 0 (medium only), 5, or 20 μg of pooled neuroantigen peptides (from myelin proteins) or ConA (non-specific mitogen) to evaluate T-cell surface markers, proliferation, and cytokine production. Compared with non-dependent controls, methamphetamine-dependent adults reported significantly higher levels of neuropsychiatric symptoms (anxiety, depression, memory). Following stimulation with neuroantigens or medium alone, a general pattern of enhanced T-cell proliferation was observed in the methamphetamine-dependent group compared with the non-dependent control group. The significant increases in T-cell proliferation were accompanied by greater in vitro production of cytokines (TNF-alpha, MIP-1beta). These results support the theory that dysregulation of immune function plays a key role in the maintenance of neuropsychiatric impairments during abstinence and that within this delicate balance of immune factors lies potential for intervention through targeted immunotherapies.
    Brain Behavior and Immunity 09/2012; 26:S25–S26. DOI:10.1016/j.bbi.2012.07.114 · 5.89 Impact Factor
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    ABSTRACT: CD40L is essential for the development of adaptive immune responses. It is generally thought that CD40L expression in CD4(+) T cells is regulated transcriptionally and made from new mRNA following antigen recognition. However, imaging studies show that the majority of cognate interactions between effector CD4(+) T cells and APCs in vivo are too short to allow de novo CD40L synthesis. We previously showed that Th1 effector and memory cells store preformed CD40L (pCD40L) in lysosomal compartments and mobilize it onto the plasma membrane immediately after antigenic stimulation, suggesting that primed CD4(+) T cells may use pCD40L to activate APCs during brief encounters. Indeed, our recent study showed that pCD40L is sufficient to mediate selective activation of cognate B cells and trigger DC activation in vitro. In this study, we show that pCD40L is present in Th1 and follicular helper T cells developed during infection with lymphocytic choriomeningitis virus, Th2 cells in the airway of asthmatic mice, and Th17 cells from the CNS of animals with experimental autoimmune encephalitis (EAE). pCD40L is nearly absent in both natural and induced Treg cells, even in the presence of intense inflammation such as occurs in EAE. We also found pCD40L expression in CD4 single positive thymocytes and invariant NKT cells. Together, these results suggest that pCD40L may function in T cell development as well as an unexpectedly broad spectrum of innate and adaptive immune responses, while its expression in Treg cells is repressed to avoid compromising their suppressive activity.
    PLoS ONE 02/2012; 7(2):e31296. DOI:10.1371/journal.pone.0031296 · 3.23 Impact Factor
  • Abigail C Buenafe ·
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    ABSTRACT: Our earlier studies described a disruption of heart rate and blood pressure diurnal rhythms in mice with experimental autoimmune encephalomyelitis (EAE). The present study investigates whether these observations could be extended to additional clock-regulated rhythms in mice with EAE. Analysis of clock gene expression in the liver of EAE mice demonstrated significant variability associated with Per2 rhythmic expression. Corticosterone and leptin hormone rhythms were also altered in EAE mice. The results presented here indicate that disturbances in clock-regulated rhythms are associated with EAE and present a suitable model for investigating the relationship between circadian disruption and autoimmune inflammatory disease.
    Journal of neuroimmunology 12/2011; 243(1-2):12-7. DOI:10.1016/j.jneuroim.2011.12.002 · 2.47 Impact Factor
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    Abigail C Buenafe · Shayne Andrew · Halina Offner · Arthur A Vandenbark ·
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    ABSTRACT: Eliciting T-cell receptor (TCR) -specific responsiveness has been known to provide an effective autoregulatory mechanism for limiting inflammation mediated by T effector cells. Our previous use of TCR peptides derived from the CDR3 regions of a pathogenic TCR effectively reversed ongoing experimental autoimmune encephalomyelitis (EAE) in a humanized TCR transgenic model. In this study, we use the TCR BV8S2 CDR2 peptide in the non-transgenic C57BL/6 EAE model to down-regulate the heterogeneous TCR BV8S2(+)  MOG-35-55-specific pathogenic T-cell population and demonstrate successful treatment of EAE after disease onset. Suppression of disease was associated with reduced MOG-35-55-specific and non-specific T-cell production of interleukin-17a and interferon-γ in the central nervous system, as well as reduced numbers of CD4(+) and Foxp3(+) T cells in the central nervous system. With the use of Foxp3-GFP and Foxp3 conditional knockout mice, we demonstrate that the TCR CDR2 peptide treatment effect is dependent on the presence of Foxp3(+) regulatory T cells and that regulatory T cell numbers are significantly expanded in the periphery of treated mice. Hence, TCR CDR2 peptide therapy is effective in regulating heterogeneous, pathogenic T-cell populations through the activity of the Foxp3(+) regulatory T cell population.
    Immunology 10/2011; 135(2):168-79. DOI:10.1111/j.1365-2567.2011.03531.x · 3.80 Impact Factor
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    ABSTRACT: T-cell receptor (TCR)-derived peptides are recognized by the immune system and are capable of modulating autoimmune responses. Using the myelin basic protein (MBP) TCR 1501 transgenic mouse model, we demonstrated that TCR CDR3 peptides from the transgenic TCR can provide a protective effect when therapy is initiated before the induction of experimental autoimmune encephalomyelitis (EAE). More importantly, TCR CDR3 peptide therapy can ameliorate the disease when administered after EAE onset. Concurrent with the therapeutic effects, we observed reduced T-cell proliferation and reduced interleukin-2 (IL-2) levels in response to stimulation with MBP-85-99 peptide in splenocyte cultures from mice receiving TCR CDR3 peptides compared with that of control mice. Moreover, we found that Foxp3(+) CD4 T cells from mice protected with TCR CDR3 peptide are preferentially expanded in the presence of IL-2. This is supportive of a proposed mechanism where Foxp3(+) T-regulatory cells induced by therapy with MBP-85-99 TCR CDR3 peptides limit expansion and the encephalitogenic activity of MBP-85-99-specific T cells by regulating the levels of secreted IL-2.
    Immunology 05/2010; 130(1):114-24. DOI:10.1111/j.1365-2567.2009.03218.x · 3.80 Impact Factor
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    Abigail C Buenafe · Courtney Sherwood · Nicole Moes · Richard E Jones ·
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    ABSTRACT: We pursued a breeding strategy intended to generate disease-resistant mice with exclusive expression of the H-2(u)-restricted myelin basic protein (MBP) 1-11 peptide-specific transgenic (Tg) T-cell receptor (TCR) on the T-cell-deficient RAG1KO (H-2(b)) background. Utilizing specific screening assays for the offspring, analyses of the F1 intercross and subsequent crosses revealed that the TgTCR-associated clonotypic marker detected by the 3H12 mAb could be found only in association with the H-2(b) homozygous background in offspring possessing a functional rag1 gene. Moreover, expression of the MBP-specific TgTCR could not be found in H-2(b) homozygous offspring that were RAG1 deficient (rag1(-/-)). PCR analysis of genomic DNA from these 3H12-negative offspring verified the presence of the TCR transgenes. Thus, the presence of a functional rag1 gene was required for the expression of the MBP-specific TgTCR on the H-2(b) background. Given the role for RAG1, the results have important implications for T-cell repertoire development.
    Journal of Neuroscience Research 01/2009; 87(1):42-9. DOI:10.1002/jnr.21839 · 2.59 Impact Factor
  • Abigail C Buenafe · Heather Zwickey · Nicole Moes · Barry Oken · Richard E Jones ·
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    ABSTRACT: Dysfunction of the autonomic nervous system may be an important component of disease progression in multiple sclerosis (MS), a paralytic inflammatory autoimmune disease of the central nervous system. Using the experimental autoimmune encephalomyelitis mouse model of MS, the authors carried out a pilot study to investigate whether telemetric monitoring might be a feasible approach for detecting disturbances in the autonomic control of heart rate and blood pressure after disease induction. Telemetric monitoring devices that were implanted in mice provided useful information regarding the physiologic changes that accompanied disease induction and progression. Changes were observed in heart rate, blood pressure, heart rate variability and diurnal rhythm immediately before and after disease onset. The device implantation procedure did not seem to alter the course of disease. Further investigation may establish these methods as a system for studying the relationships between MS progression and autonomic regulation of physiological status.
    Lab Animal 08/2008; 37(8):361-8. DOI:10.1038/laban0808-361 · 0.74 Impact Factor
  • Abigail C Buenafe · Dennis N Bourdette ·
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    ABSTRACT: Treatment with the bacterial product lipopolysaccharide (LPS) prior to the induction of experimental autoimmune encephalomyelitis (EAE) consistently led to a delayed onset of disease but not to a reduction in disease severity. T cell proliferation was reduced in LPS-treated mice, due at least in part to a loss in antigen presenting cell function. T cell and macrophage infiltration into the CNS was delayed and TNFalpha production was diminished in LPS pre-treated mice, consistent with the delay in disease onset. Real-time PCR analysis of gene expression in the CNS of LPS or saline pre-treated mice demonstrated an early induction of TNFalpha, TGFbeta, IFNbeta, and SOCS3 in the LPS pre-treated mice. Thus, exposure to LPS prior to EAE induction affects antigen presentation and may modulate the expression of inflammatory regulators that impact the autoimmune disease course.
    Journal of Neuroimmunology 02/2007; 182(1-2):32-40. DOI:10.1016/j.jneuroim.2006.09.004 · 2.47 Impact Factor
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    ABSTRACT: The goal of this study was to establish an unlimited and standardized source of humanized myelin peptide-specific T cells for in vitro testing of biological function. Thus, we perpetuated myelin oligodendrocyte glycoprotein (MOG)-35-55 peptide-specific T cells obtained from immunized HLA-DRB1*1501-transgenic (Tg) mice by somatic fusions with BW5147 thymoma cells or BW5147 T-cell receptor (TCR) alpha(-)beta(-) variant (BW5147 variant) cells. The resulting T-cell hybridomas responded strongly to both mouse MOG-35-55 (42S) and human MOG-35-55 peptide (42P), regardless of which peptide was used for initial immunization, and were DRB1*1501 restricted. The MOG-35-55-reactive T-cell hybridomas were CD3(+)CD4(+)CD8(-) and expressed intracellular Th1 cytokines upon concanavalin A stimulation. Clones from either human MOG-35-55- or mouse MOG-35-55-selected hybridomas uniquely expressed the TCR BV8 gene in combination with AV17 and AV11 genes. V gene analyses confirmed the expression of TCR AV1, AV11, AV16, BV1, and BV5 gene segments in the widely used fusion partner BW5147 and demonstrated deletion of TCR AV1, AV11, and BV1 in the BW5147 variant. T-cell hybridomas were positively stained with anti-TCR beta-chain antibody on the cell surface, whereas neither BW5147 nor its variant had positive TCR surface expression. For functional application, we found that a monomeric form of the human HLA-DR2-derived recombinant T-cell receptor ligand (RTL) covalently linked to human MOG-35-55 peptide specifically inhibited proliferation of a hybridoma clone selected with human MOG-35-55 but not a different hybridoma clone selected with myelin basic protein. The RTL-induced inhibition in vitro of the human MOG-35-55 peptide-specific hybridoma reflected the ability of the RTL to inhibit experimental autoimmune encephalomyelitis induced by human MOG-35-55 peptide in HLA-DR2 transgenic mice. Thus, the MOG-35-55 peptide-specific T-cell hybridoma from DR2-Tg mice represents a novel humanized T-cell reagent useful for standardized biological screening of both DR2-restricted stimulation and RTL-dependent inhibition of response to human MOG-35-55 peptide.
    Journal of Neuroscience Research 09/2004; 77(5):670-80. DOI:10.1002/jnr.20201 · 2.59 Impact Factor
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    ABSTRACT: Although the phenotypic and regulatory properties of the CD4(+)CD25(+) T cell lineage (Treg cells) have been well described, the specificities remain largely unknown. We demonstrate here that the CD4(+)CD25(+) Treg population includes the recognition of a broad spectrum of human TCR CDR2 determinants found in the germline V gene repertoire as well as that of a clonotypic nongermline-encoded CDR3beta sequence present in a recombinant soluble T cell receptor (TCR) protein. Regulatory activity was demonstrated in T cell lines responsive to TCR but not in T cell lines responsive to control antigens. Inhibitory activity of TCR-reactive T cells required cell-cell contact and involved CTLA-4, GITR, IL-10, and IL-17. Thus, the T-T regulatory network includes Treg cells with specificity directed toward self-TCR determinants.
    Journal of Neuroscience Research 04/2004; 76(1):129-40. DOI:10.1002/jnr.20066 · 2.59 Impact Factor
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    ABSTRACT: The encephalitogenic rat T cell clone C14 recognizes the myelin basic protein 69-89 peptide in the context of the RT1B major histocompatibility complex (MHC) class II molecule. Modeling of the C14 TCR molecule indicated that previously identified CDR3 motifs are likely to be central to interaction with MHC class II-presented peptide. Here we report the cloning and expression of C14-derived single chain TCR (scTCR) molecules in an Escherichia coli expression system. The recombinant molecule consists of the Valpha2 domain connected to the Vbeta8.2 domain via a 15-residue linker. Soluble C14 scTCR was purified using conventional chromatography techniques and refolded by a rapid dilution procedure. C14 scTCR was able to bind soluble rat MHC class II molecules bearing covalently coupled Gp-BP-(69-89) peptide, as analyzed using surface plasmon resonance. Immune recognition of the C14 scTCR protein as an antigen revealed that limited regions of the TCR may be more likely to induce responsiveness.
    Journal of Biological Chemistry 09/2003; 278(33):30961-70. DOI:10.1074/jbc.M300628200 · 4.57 Impact Factor
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    ABSTRACT: To investigate regulatory mechanisms which naturally prevent autoimmune diseases, we adopted the genetically restricted immunodeficient (RAG-1(-/-)) myelin basic protein (MBP)-specific T cell receptor (TCR) double transgenic (T/R-) mouse model of spontaneous experimental autoimmune encephalomyelitis (Sp-EAE). Sp-EAE can be prevented after transfer of CD4+splenocytes from naïve immunocompetent mice. RAG-1+ double transgenic (T/R+) mice do not develop Sp-EAE due to the presence of a very small population (about 2%) of non-Tg TCR specificities. In this study, CD4+BV8S2+ T cells that predominate in T/R+ mice, and three additional populations, CD4+BV8S2-, CD4-CD8-BV8S2+, and CD4-CD8+BV8S2+ T cells that expanded in T/R+ mice after immunization with MBP-Ac1-11 peptide, were studied for their ability to prevent Sp-EAE in T/R- mice. Only the CD4+BV8S2- T cell population conferred complete protection against Sp-EAE, similar to unfractionated splenocytes from non-Tg donors, whereas CD4-CD8-BV8S2+ and CD4+BV8S2+ T cells conferred partial protection. In contrast, CD4-CD8+BV8S2+ T cells had no significant protective effects. The highly protective CD4+BV8S2- subpopulation was CD25+, contained non-clonotypic T cells, and uniquely expressed the CCR4 chemokine receptor. Protected recipient T/R- mice had marked increases in CD4+CD25+ Treg-like cells, retention of the pathogenic T cell phenotype in the spleen, and markedly reduced inflammation in CNS tissue. Partially protective CD4+BV8S2+ and CD4- CD8-BV8S2+ subpopulations appeared to be mainly clonotypic T cells with altered functional properties. These three Sp-EAE protective T cell subpopulations possessed distinctive properties and induced a variety of effects in T/R- recipients, thus implicating differing mechanisms of protection.
    Journal of Neuroscience Research 01/2003; 71(1):89-103. DOI:10.1002/jnr.10450 · 2.59 Impact Factor
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    ABSTRACT: Estrogen has been found to have suppressive effects on the induction of experimental autoimmune encephalomyelitis (EAE), an animal model for the human disease multiple sclerosis. We have investigated the effects of 17beta-estradiol (E2) treatment on dendritic cells (DCs) in two different mouse models of EAE. The frequency of CD11b(+)/CD11c(+) DCs was significantly decreased in the brain of mice protected from EAE induction by E2 treatment. In addition, the frequency of CD11c(+)/CD8alpha(+) DCs producing tumor necrosis factor (TNF)alpha and interferon (IFN)gamma in the spleen of E2-treated mice was dramatically decreased compared to that in control mice with EAE, demonstrating an effect of E2 on DC function. In order to examine E2 effects on DCs in more detail, splenic DCs were cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 to promote maturation. E2 pretreatment was found to suppress the ability of cultured DCs bearing a mature phenotype to present Ag to myelin basic protein (MBP)-specific T cells. Analysis of cytokine production demonstrated that E2 decreased TNFalpha, IFNgamma and IL-12 production in mature DCs. In addition, MBP-specific T cells cocultured with E2-pretreated mature DCs in the presence of antigen demonstrated a shift towards production of Th2 cytokines IL-4 and IL-10 and a concomitant decrease in the production of Th1 cytokines TNFalpha and IFNgamma. Thus, E2 treatment appears to have multiple effects on the DC population, which may contribute to a down-regulation or block in the activation of Th1 cells involved in the induction of EAE.
    Journal of Neuroscience Research 10/2002; 70(2):238-48. DOI:10.1002/jnr.10409 · 2.59 Impact Factor
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    ABSTRACT: Estrogen treatment has been found to have suppressive activity in several models of autoimmunity. To investigate the mechanism of 17 beta-estradiol (E2) suppression of experimental autoimmune encephalomyelitis, we evaluated E2 effects on TNF-alpha expression in the central nervous system (CNS) and spleen of C57BL/6 mice immunized with MOG 35-55/CFA. Kinetic analysis demonstrated that E2 treatment drastically decreased the recruitment of total inflammatory cells as well as TNF-alpha(+) macrophages and T cells into the CNS at disease onset. In contrast, E2 had only moderate effects on the relatively high constitutive TNF-alpha expression by resident CNS microglial cells. E2 treatment also had profound inhibitory effects on expression of TNF-alpha by splenic CD4(+) T cells, including those responsive to MOG 35-55 peptide. We propose that the mechanism of E2 protection may involve both systemic inhibition of TNF-alpha expression and local (CNS) recruitment of inflammatory cells, with modest effects on TNF-alpha expression by resident CNS microglial cells.
    Clinical Immunology 04/2002; 102(3):275-82. DOI:10.1006/clim.2001.5175 · 3.67 Impact Factor
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    ABSTRACT: The genes encoding the Lewis rat RT1.B molecule (MHC Class II I-A equivalent) were transfected and expressed in mouse DAP.3 fibroblast cells together with the gene encoding the mouse ICAM-1 molecule. Both molecules were stably expressed on the cell surface of DAP.3 cells under longterm culture conditions. The RT1.B/mICAM-1 transfectants presented antigen in a specific manner to a RT1. B-restricted rat T cell hybridoma specific for the 69-89 peptide of myelin basic protein (BP). In addition, the transfectants were able to present antigen to a BP69-89-specific rat T cell line. Presentation to a RT1.D (MHC Class II I-E equivalent)-restricted BP87-99-specific T cell line was minimal. Production of the Th1 cytokine IFN-gamma by BP69-89-specific T cells when stimulated by RT1.B/mICAM-1 transfectants correlated very well with proliferation to specific antigen. Moreover, RT1.B-transfected DAP.3 cells sufficiently stimulated BP69-89-specific T cells such that they were able to transfer experimental autoimmune encephalomyelitis (EAE) to Lewis rat recipients. Thus, the RT1.B molecule is functionally expressed on the surface of transfected Dap.3 fibroblasts and is capable of MHC Class II-restricted, antigen-specific presentation to rat T cells.
    Journal of Neuroimmunology 02/2001; 112(1-2):106-14. DOI:10.1016/S0165-5728(00)00390-8 · 2.47 Impact Factor
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    ABSTRACT: The major function of the T-cell receptor is to confer antigen specificity to T cells. However, nascent TCR proteins that are not assembled into functional heterodimers may be processed and displayed with self MHC molecules on the T-cell surface, and are thought to be the genesis of autoregulatory T cells that can limit inflammatory responses through T-T network interactions. In previous work, we and others have exploited this natural regulatory system using TCR peptides to amplify regulatory T cells that potentially can treat human autoimmune diseases such as multiple sclerosis (MS) and arthritis. The development of this approach is limited by the diversity of human TCR V gene sequences, and by lack of knowledge of exactly which regions of the V gene proteins are immunogenic in association with various MHC alleles. To identify similar amino acid sequences within and among human V gene families that might have immunologic cross reactivity, we aligned 74 known AV and 109 known BV protein sequences into homologous groups using the ClustalX program. Moreover, with a focus on CDR2 peptides that have previously been used to induce regulatory T cells in clinical trials, we established homologous peptide groups, and then identified the optimal amino acid motifs for binding to two alleles, HLA-DRB1*1501 and DRB5*0101, that have been associated with susceptibility to MS. From this analysis, > 75% of AV and BV CDR2 sequences were predicted to bind with at least moderate avidity to each of the DR2 alleles, thus enhancing the likelihood that they could be antigenic. Further ordering of putative TCR contact residues revealed a different set of homology groupings, including many intrafamily sequence matches and some interfamily matches that might allow immunological cross reactivity. Particularly striking were DRB1*1501-restricted IH-S and IY-S motifs shared by BV11, BV12, and BV13 and BV3, BV12, BV13, and BV17 family members, respectively, and DRB5*0101-restricted RL-H and RL-Y motifs shared by BV11, BV12, and BV13 and BV13 and BV17 family members, respectively. This analysis may be useful in designing an array of clinically useful homologous peptides with optimal MHC binding properties and highly cross-reactive TCR binding motifs.
    Critical Reviews in Immunology 01/2000; 20(1):57-83. DOI:10.1615/CritRevImmunol.v20.i1.30 · 3.70 Impact Factor
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    ABSTRACT: Interleukin-7 has demonstrated potent enhancing effects on the growth and differentiation of several immature cell types, including thymocytes, and on survival of resting and antigen activated T cells. In this study, we evaluated the effects of IL-7 on post-thymic antigen-specific T cells from human blood. IL-7 was found to enhance proliferation responses and IFN-gamma secretion of myelin or recall Ag-specific Th1 cells through the selective up-regulation of the IL-2Ralpha and gamma but not beta chains in both an Ag-dependent and Ag-independent manner, but did not affect monocytes, B cells, or NK cells. These functions of IL-7 enhanced the detection of Th1 but not Th2 cell frequency by >2.5 fold, and promoted selection of Ag-specific Th1 cells by the limiting dilution method. Moreover, IL-7 pretreatment conferred increased resistance of CD4+ T cells to CD8+ cell lysis. These studies demonstrate that IL-7 promotes the growth and survival of circulating Ag-specific human Th1 cells through a mechanism that probably involves the gammac common receptor for IL-2 family members that includes IL-7.
    Journal of Neuroimmunology 04/1999; 96(1):101-11. · 2.47 Impact Factor
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    ABSTRACT: Interleukin-7 has demonstrated potent enhancing effects on the growth and differentiation of several immature cell types, including thymocytes, and on survival of resting and antigen activated T cells. In this study, we evaluated the effects of IL-7 on post-thymic antigen-specific T cells from human blood. IL-7 was found to enhance proliferation responses and IFN-γ secretion of myelin or recall Ag-specific Th1 cells through the selective up-regulation of the IL-2Rα and γ but not β chains in both an Ag-dependent and Ag-independent manner, but did not affect monocytes, B cells, or NK cells. These functions of IL-7 enhanced the detection of Th1 but not Th2 cell frequency by >2.5 fold, and promoted selection of Ag-specific Th1 cells by the limiting dilution method. Moreover, IL-7 pretreatment conferred increased resistance of CD4+ T cells to CD8+ cell lysis. These studies demonstrate that IL-7 promotes the growth and survival of circulating Ag-specific human Th1 cells through a mechanism that probably involves the γc common receptor for IL-2 family members that includes IL-7.
    Journal of Neuroimmunology 04/1999; 96(1):101-111. DOI:10.1016/S0165-5728(99)00002-8 · 2.47 Impact Factor
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    H Offner · K Adlard · B.F. Bebo · J Schuster · G.G. Burrows · A.C. Buenafe · A A Vandenbark ·
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    ABSTRACT: TCR determinants overexpressed by autopathogenic Th1 cells can naturally induce a second set of TCR-specific regulatory T cells. We addressed the question of whether immune regulation could be induced naturally in a genetically restricted model in which a major portion of TCR-specific regulatory T cells expressed the same target TCR BV8S2 chain as the pathogenic T cells specific for myelin basic protein (MBP). We found vigorous T cell responses to BV8S2 determinants in naive mice that could be further potentiated by vaccination with heterologous BV8S2 proteins, resulting in the selective inhibition of MBP-specific Th1 cells and protection against experimental encephalomyelitis. Moreover, coculture with BV8S2-specific T cells or their supernatants reduced proliferation, IFN-gamma secretion, and encephalitogenic activity of MBP-specific T cells. These results suggest that immune regulation occurs through a nondeletional cytokine-driven suppressive mechanism.
    The Journal of Immunology 10/1998; 161(5):2178-86. DOI:10.1016/S0165-5728(98)91535-1 · 4.92 Impact Factor

Publication Stats

996 Citations
179.17 Total Impact Points


  • 2012
    • Portland VA Medical Center
      Portland, Oregon, United States
  • 1986-2012
    • Oregon Health and Science University
      • • Department of Neurology
      • • Department of Molecular Microbiology & Immunology
      Portland, OR, United States
  • 1993-1994
    • United States Department of Veterans Affairs
      Бедфорд, Massachusetts, United States