Clonal dominance among T-lymphocyte infiltrates in arthritis.

Stamenkovic, Ivan; Stegagno, M; Wright, Kathryn; Krane, Stephen M.; Amento, Edward P.; Colvin, Robert B.; Duquesnoy, René J.; Kurnick, James T.

doi:10.1073/pnas.85.4.1179

Cited by 239 publications

(105 citation statements)

References 37 publications

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“…This raises the possibility of using superantigens as tolerogens to inactivate subpopulations of T cells that express TCR with common features. This approach would be of particular relevance in certain autoimmune diseases where the diversity of TCR is limited (30,31 …”

Section: Discussionmentioning

confidence: 99%

Induction of specific clonal anergy in human T lymphocytes by Staphylococcus aureus enterotoxins.

O’Hehir¹,

Lamb²

1990

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

121

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The exotoxins produced by certain strains of Staphylococcus aureus are able to stimulate powerful polyclonal proliferative responses and to induce nonresponsiveness by clonal deletion of T lymphocytes expressing the appropriate T-cell antigen receptor VP gene products. This paper examines the ability of S. aureus enterotoxins to modulate the responsiveness of human CD4' T lymphocytes with defined antigen specificity. It was observed that certain S. auress toxins were able to activate and induce anergy in hemagglutinin-reactive T cells expressing V133 elements. After exposure to S. aureus enterotoxins A, B, and D in the absence of antigen-presenting cells, the T cells failed to respond to their natural ligand presented in an immunogenic form, despite enhanced proliferation to exogenous interleukin 2. The S. aureus toxin-induced anergy was associated with modulation of T-cell membrane receptors; down-regulation of the T-cell antigen receptor was concomitant with enhanced expression of CD2 and CD25. Interestingly, CD28 was increased only on stimulation, suggesting this protein may be differentially expressed by activated and anergic T cells. These results indicate that bacterial toxins are able to induce antigen-specific nonresponsiveness in human T cells, the application of which may be relevant in the regulation of T cells expressing a particular family of VP gene products.The staphylococcal enterotoxins (1, 2) and certain endogenously derived proteins such as MIs (3, 4) are members of a family of antigens termed "superantigens," based on their ability to stimulate powerful polyclonal proliferative responses of murine and human T lymphocytes bearing particular T-cell antigen receptor (TCR) Vj3 gene products (4-7). Additionally, superantigens are also able to induce nonresponsiveness in murine T cells either by clonal deletion (5) or functional inactivation (8). With the development of in vitro experimental systems, it has been possible to demonstrate that occupancy of the TCR by peptidic fragments of antigen complexed with class II major histocompatibility complex (MHC) molecules, in the absence of additional signals (costimulatory activity), is able to induce antigen-specific anergy (9-12). However, direct evidence to support clonal anergy as an operational mechanism in the development and maintenance of tolerance to either self or extrinsic antigens in vivo has been difficult to obtain. The results of recent experiments examining T-cell tolerance to nonlymphoid-expressed MHC molecules (13,14) or to the self superantigen Mls-la (8) suggest that nonresponsiveness, in certain instances, may be accounted for by functional inactivation. Similarity between the functional characteristics of these in vivo experimental models and those of peptide-specific T-cell anergy induced in vitro (9-12) prompted us to investigate the ability of Staphylococcus aureus enterotoxins to induce antigen-specific nonresponsiveness in cloned human CD4' T cells specific for the carboxyl terminus of influenza virus hemagglutinin (HA)...

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Section: Discussionmentioning

confidence: 99%

Induction of specific clonal anergy in human T lymphocytes by Staphylococcus aureus enterotoxins.

O’Hehir¹,

Lamb²

1990

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

121

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“…Several lines of evidence suggest that T cells that infiltrate the RA synovium play an important role in the initiation and perpetuation of the disease process (16). These cells recognize a certain antigen presented on major histocompatibility complex (MHC) molecules, and then proliferate oligoclonally in response to antigen stimulation (17)(18)(19). These antigen-specific T cells seem to induce polyclonal T cell activation, which leads to chronic inflammation.…”

mentioning

confidence: 99%

Evidence for autoantigens of Env/Tax proteins in human T cell leukemia virus type I Env-pX transgenic mice

Fujisawa

Okamoto

Asahara

et al. 1998

Arthritis & Rheumatism

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Objective. To examine T cell clonotypes infiltrating into arthritic joints and to investigate whether human T cell leukemia virus type I (HTLV-I) env-pX gene products act as autoantigens in HTLV-I env-pX transgenic mice.Methods. Complementary DNA (cDNA) encoding the V-D-J (third complementarity-determining region[CDR3]) region of T cell receptor p chain was amplified by Vp family polymerase chain reaction. T cell clonotypes were detected by a single-strand conformational polymorphism method, and sequence analysis of the CDR3 region was performed.Results. Distinct oligoclonal T cell expansion was observed in arthritic joints, and a conserved amino acid motif in the CDR3 region was found in T cells infiltrating joints. Moreover, several intraarticular T cells recognized HTLV-I Env and Tax proteins.Conclusion. Our results suggest that HTLV-I Env and Tax proteins act as autoantigens that are recognized by autoreactive T cells in inflamed arthritic lesions in the HTLV-I env-pX transgenic mouse. Thus, some T cells infiltrating the joint recognize Env or Tax protein. These cells may trigger chronic arthritis in HTLV-I env-pX transgenic mice.Human T cell leukemia virus type I (HTLV-I), the etiologic agent of adult T cell leukemia (1), is also

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“…of MHC molecules (26,27). There are also reports of common V gene usage in autoimmune responses where the antigens involved are still undefined (28,29). The involvement of RadLV env gene products in the binding interaction of lymphoma cells with free virus particles has been reported (6,30,31).…”

Section: Resultsmentioning

confidence: 99%

A murine retrovirus induces proliferation of unique lymphoid cell lines expressing T-cell-receptor structures utilizing common variable region alpha and beta chain genes.

O’Neill¹

1993

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

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A murine radiation leukemia virus (RadLV) has been shown to induce in vitro proliferation of an unusual subset of lymphoid cells from spleen. They have the unusual property of expressing CD3/T-cell receptor a and ,B chains (TCR-a,l) in the absence ofother T-cell markers such as Thy-i, CD4, and CD8. Cell lines induced in two mouse strains with RadLV produced by the C6VL/1 thymoma all specifically utilize common Va3 and V.88.2 variable region genes in the formation of a TCR structure. Each of these cell lines has now been found to express both class I and dass II major histo-

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Clonal dominance among T-lymphocyte infiltrates in arthritis.

Cited by 239 publications

References 37 publications

Induction of specific clonal anergy in human T lymphocytes by Staphylococcus aureus enterotoxins.

Induction of specific clonal anergy in human T lymphocytes by Staphylococcus aureus enterotoxins.

Evidence for autoantigens of Env/Tax proteins in human T cell leukemia virus type I Env-pX transgenic mice

A murine retrovirus induces proliferation of unique lymphoid cell lines expressing T-cell-receptor structures utilizing common variable region alpha and beta chain genes.

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