Clonally expanded V?12+ (AV12S1),CD8+ T cells from a patient with rheumatoid arthritis are autoreactive

Behar, Samuel M.; Roy, Chris; Lederer, James A.; Fraser, Pat; Brenner, Michael B.

doi:10.1002/1529-0131(199803)41:3<498::aid-art16>3.0.co;2-4

Cited by 11 publications

(3 citation statements)

References 29 publications

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“…In tap1 -deficient mice, this defect in the class I MHC antigenprocessing pathway results in greatly reduced numbers of CD8 ϩ T cells in all lymphoid organs, as CD8 ϩ T cells are not positively selected during T cell maturation in the thymus (23). In contrast, TAP deficiency is not believed to lead to a deficiency of CD1-restricted T cells, as all examples of CD1-restricted antigen recognition by T cells have been determined to be TAP independent (17,24,25). We therefore felt that the TAP1-deficient (TAP1 ϪրϪ ) and CD1D -deficient (CD1D ϪրϪ ) mice would be important independent models to determine the significance of CD8 ϩ T cells in immunity to M .…”

mentioning

confidence: 99%

Susceptibility of Mice Deficient in CD1D or TAP1 to Infection with Mycobacterium tuberculosis

Behar

Dascher

Grusby

et al. 1999

The Journal of Experimental Medicine

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325

233

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Cellular immunity against Mycobacterium tuberculosis controls infection in the majority of infected humans. Studies in mice have delineated an important role for CD4+ T cells and cytokines including interferon γ and tumor necrosis factor α in the response to infection with mycobacteria. Recently, the identification of CD8+ CD1-restricted T cells that kill M. tuberculosis organisms via granulysin and the rapid death after infection of β2 microglobulin deficient mice in humans has drawn attention to a critical role for CD8+ T cells. The nature of mycobacterial-specific CD8+ T cells has been an enigma because few have been identified in any species. Here, we delineate the contribution of class I MHC–restricted T cells in the defense against tuberculosis as transporter associated with antigen processing (TAP)1-deficient mice died rapidly, bore a greater bacterial burden, and had more severe tissue pathology than control mice. In contrast, CD1D−/− mice were not significantly different in their susceptibility to infection than control mice. This data demonstrates a critical role for TAP-dependent peptide antigen presentation and provides further evidence that class I MHC–restricted CD8+ T cells, the major T cell subset activated by this antigen processing pathway, play an essential role in immunity to tuberculosis.

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mentioning

confidence: 99%

Susceptibility of Mice Deficient in CD1D or TAP1 to Infection with Mycobacterium tuberculosis

Behar

Dascher

Grusby

et al. 1999

The Journal of Experimental Medicine

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325

233

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“…HLA-B27ϩ patients with spondylarthropathies show abnormal T and B cell responses to the epitopes shared by the HLA-B27 and peptides derived from Klebsiella pneumoniae and Shigella flexneri (15)(16)(17)(18). In addition, in patients with RA, HLA class I-restricted CD8ϩ T cell clones reactive with self HLA-DQ2 have been described (19). Moreover, IgM rheumatoid factor has been shown to react with HLA class I molecules (20).…”

Section: Discussionmentioning

confidence: 99%

Proinflammatory responses to self HLA epitopes are triggered by molecular mimicry to Epstein‐Barr virus proteins in oligoarticular juvenile idiopathic arthritis

Massa¹,

Mazzoli²,

Pignatti³

et al. 2002

Arthritis & Rheumatism

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Objective. To evaluate whether abnormal T cell recognition may be generated by exposure to exogenous antigens presenting sequence homology with epitopes contained in self HLA alleles, and if such recognition may be part of the mechanisms that fuel inflammation in autoimmune diseases associated with certain HLA alleles.Methods. Cytotoxic responses of peripheral blood mononuclear cells to 9-mer peptides derived from HLA molecules (DRB1*1101, DRB1*0801, or DPB1*0201) associated with oligoarticular juvenile idiopathic arthritis (JIA) or homologous peptides derived from EpsteinBarr virus (EBV) proteins (Bolf1 or Balf2) were analyzed in patients with oligoarticular JIA and in healthy controls matched for HLA-DRB1*1101, DRB1*0801, or DPB1*0201. Production of proinflammatory cytokines in culture supernatants was determined by enzymelinked immunosorbent assay.Results. T cell cytotoxic responses and production of proinflammatory cytokines in response to stimulation with self HLA-derived peptides were found only in patients with oligoarticular JIA, and not in controls.Patients with oligoarticular JIA, but none of the healthy controls, had EBV-self HLA cross-reactive T cells.Conclusion. Our data suggest a disease-and allele-specific mechanism of autoimmunity in oligoarticular JIA. This mechanism may be part of the pathogenesis of the disease, and could be the basis of one of the likely multiple candidates for antigen-specific immunotherapy approaches in the future.

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“…Increased homeostatic proliferation may thus ultimately lead to the presence of a T-cell pool with contracted TCR repertoire and high affinity TCRs for self-antigens. In RA-patients, large clones of CD4 + and CD8 + T-cells were found in peripheral blood and these clones were reactive with self-antigens [28][29][30][31].…”

Section: Increased Peripheral Turnover Leads To Telomere Loss and Redmentioning

confidence: 99%

Early Aged T-Cells in Immune-Mediated Diseases

Duftner¹,

Dejaco²,

Schirmer

2011

CIR

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Early loss of thymic function may be crucial for the development of immune-mediated diseases. According to this concept premature collapse of thymic output is compensated by homeostatic proliferation of peripheral T-cells, driven by recognition of self antigens and finally resulting in the expansion of autoreactive, senescent T-cell clones. Such senescent T-cells are characterized by the loss of the co-stimulatory receptor CD28 and the gain of new immunomodulatory molecules such as natural killer cell receptors and toll-like receptors. The immune system may compensate for these changes by regulatory mechanisms, including the evolvement of regulatory T-cells. However, the aging process may also affect these regulatory T-cells leading to a second "hit" of the immune system. Current therapeutic approaches in patients with immune-mediated diseases target common end pathways of inflammation, driven by proinflammatory cytokines and effector cells. Future directions will include the aim to reset the immune system, by restoring the ability to repopulate the immune system with young and adaptable lymphocytes as well as by strengthening the effect of regulatory T-cells.

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Clonally expanded V?12+ (AV12S1),CD8+ T cells from a patient with rheumatoid arthritis are autoreactive

Cited by 11 publications

References 29 publications

Susceptibility of Mice Deficient in CD1D or TAP1 to Infection with Mycobacterium tuberculosis

Susceptibility of Mice Deficient in CD1D or TAP1 to Infection with Mycobacterium tuberculosis

Proinflammatory responses to self HLA epitopes are triggered by molecular mimicry to Epstein‐Barr virus proteins in oligoarticular juvenile idiopathic arthritis

Early Aged T-Cells in Immune-Mediated Diseases

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