Polymyositis Mediated by T Lymphocytes That Express the γ/δ Receptor

Hohlfeld, Reinhard; Engel, Andrew G.; Ii, Kunio; Harper, Michel C.

doi:10.1056/nejm199103283241303

Cited by 143 publications

(90 citation statements)

References 26 publications

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“…The different cell populations can be distinguished only by morphological criteria, i.e., by single-cell analysis. Only in very rare cases of monoclonal expansions (24)(25)(26)(27) can paired TCR chains be identified from tissue homogenates. Early pioneering studies described the Ig repertoire of B cells in single-cell experiments (28), but unbiased amplification from single-tissue-infiltrating T cells has so far been achieved only for TCR ␤-chains (7,8,29).…”

Section: Discussionmentioning

confidence: 99%

Reconstitution of paired T cell receptor α- and β-chains from microdissected single cells of human inflammatory tissues

Seitz

Schneider

Malotka

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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We describe a strategy to ''revive'' putatively pathogenic T cells from frozen specimens of human inflammatory target organs. To distinguish pathogenic from irrelevant bystander T cells, we focused on cells that were (i) clonally expanded and (ii) in direct morphological contact with a target cell. Using CDR3 spectratyping, we identified clonally expanded T cell receptor (TCR) ␤-chains in muscle sections of patients with inflammatory muscle diseases. By immunohistochemistry, we identified those V␤-positive T cells that fulfilled the morphological criteria of myocytotoxicity and isolated them by laser microdissection. Next, we identified coexpressed pairs of TCR ␣-and ␤-chains by a multiplex PCR protocol, which allows the concomitant amplification of both chains from single cells. This concomitant amplification had not been achieved previously in histological sections, mainly because of the paucity of available anti-␣-chain antibodies and the great heterogeneity of the ␣-chain genes. From muscle tissue of a patient with polymyositis, we isolated 64 T cells that expressed an expanded V␤1 chain. In 23 of these cells, we identified the corresponding ␣-chain. Twenty of these 23 ␣-chains were identical, suggesting antigendriven selection. After functional reconstitution of the ␣␤-pairs, their antigen-recognition properties could be studied. Our results open avenues for combined analysis of the full TCR ␣-and ␤-chain repertoire in human inflammatory tissues.autoimmunity ͉ immunopathology ͉ myositis ͉ repertoire ͉ single-cell PCR

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Section: Discussionmentioning

confidence: 99%

Reconstitution of paired T cell receptor α- and β-chains from microdissected single cells of human inflammatory tissues

Seitz

Schneider

Malotka

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…A striking example of a putatively autoimmune human ␥␦-TCR 2 was described in 1991 (8). This ␥␦-TCR was isolated from muscle of a unique but well characterized patient with ␥␦-T cell-mediated myositis.…”

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confidence: 99%

Target Specificity of an Autoreactive Pathogenic Human γδ-T Cell Receptor in Myositis

Bruder

Siewert

Obermeier

et al. 2012

Journal of Biological Chemistry

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Background:In a rare case of human autoimmune myositis, muscle fibers are attacked by ␥␦-T cells. Results: We identified several antigens recognized by the ␥␦-T cell receptor. Conclusion:The ␥␦-T cell receptor recognized human tRNA synthetases known as antigens of autoantibodies in myositis. Significance: This is the first report of an antigen recognized by human ␥␦-T cells in an autoimmune disease.

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“…However, other cd TCRs are diverse initially, and later selected during immune responses. 5,6 At the level of lymphocyte populations, the cd TCRs appear to be less evenly distributed than the other adaptive receptors. In mice, where this has been studied in detail, subsets of cd T cells expressing different Vcs become segregated already during ontogeny due to their sequential developmental patterns in the thymus.…”

Section: The CD T-cell Receptorsmentioning

confidence: 99%

“…This amazing story goes back to a rare case of human autoimmune myositis where infiltration of skeletal muscle with cd T cells instead of the more common autoreactive ab T cells was observed. 5 It was found that the muscle-infiltrating cd T cells were clonally expanded and express an uncommon Vc1.3Vd2 1 cd TCR. 86 Based on responses of transfectomas, as well as binding studies with soluble TCR constructs, 87,88 it appears now that this cd TCR (named M88) recognizes a common conformational motif on the surface of several proteins from different species, including bacterial and human aminoacyl-tRNA synthetases.…”

Section: Soluble Proteinsmentioning

confidence: 99%

Diversity of γδ T-cell antigens

2012

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In the last two decades, it has become clear that cd T cells recognize a diverse array of antigens including self and foreign, large and small, and peptidic and non-peptidic molecules. In this respect, cd antigens as a whole resemble more the antigens recognized by antibodies than those recognized by ab T cells. Because of this antigenic diversity, no single mechanism-such as the major histocompatibility complex (MHC) restriction of ab T cells-is likely to provide a basis for all observed T-cell antigen receptor (TCR)-dependent cd T-cell responses. Furthermore, available evidence suggests that many individual cd T cells are poly-specific, probably using different modes of ligand recognition in their responses to unrelated antigens. While posing a unique challenge in the maintenance of self-tolerance, this broad reactivity pattern might enable multiple overlapping uses of cd T-cell populations, and thus generate a more efficient immune response.

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Polymyositis Mediated by T Lymphocytes That Express the γ/δ Receptor

Abstract: Polymyositis can be mediated by gamma/delta T cells. This new form of polymyositis appears to be highly responsive to steroids.

Cited by 143 publications

References 26 publications

Reconstitution of paired T cell receptor α- and β-chains from microdissected single cells of human inflammatory tissues

Reconstitution of paired T cell receptor α- and β-chains from microdissected single cells of human inflammatory tissues

Target Specificity of an Autoreactive Pathogenic Human γδ-T Cell Receptor in Myositis

Diversity of γδ T-cell antigens

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