title: Autoreactive T cells in healthy individuals show tolerance in vitro with characteristics similar to but distinct from clonal anergy.
abstract: Peripheral tolerance to self antigens has been suspected to play an important role in the regulation of the immune response in humans since autoreactive T cells can be isolated from the peripheral blood of healthy individuals. The mechanism of this tolerance is not known, but a number of groups have shown that autoreactive T cells can be induced to proliferate in vitro by the addition of their specific antigen and exogenous interleukin (IL)-2. In this report, we present the analysis of autoreactive T cells, isolated from healthy individuals, to the autoantigen GpIIb-IIIa present on circulating bone-marrow-derived cells and on thymic epithelial cells. We found that the response of GpIIb-IIIa autoreactive T cells in vitro, when stimulated with GpIIb-IIIa, shares characteristics with the response found for anergic T cells. In response to GpIIb-IIIa, the GpIIb-IIIa-autoreactive T cells are neither able to proliferate nor produce IL-2 on their own, but do express IL-2 receptors alpha on their cell surface and produce IFN-gamma. This state of unresponsiveness can be broken by the addition of exogenous IL-2 and IL-7, as in the case of anergic T cells. However, GpIIb-IIIa-autoreactive T cells differ from anergic T cells in their capacity to be stimulated by IL-12 and by their production of IL-2 mRNA. Interestingly, once the unresponsive state to GpIIb-IIIa has been broken by the addition of IL-2, GpIIb-IIIa autoreactive T cells can produce IL-2 and proliferate when restimulated by GpIIb-IIIa alone. Altogether, these results suggest that the tolerance of GpIIb-IIIa autoreactive T cells from healthy individuals could involve post-transcriptional regulation of IL-2 expression.
mesh_terms: D015551:Autoimmunity / Q000276:immunology; D002460:Cell Line; D017635:Clonal Anergy / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000502:physiology; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D015851:Interleukin-7 / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology*; D012323:RNA Processing, Post-Transcriptional / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D007376:Interleukin-2; D015851:Interleukin-7; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D018664:Interleukin-12; D007371:Interferon-gamma