A role for antigen-presenting cells and bacterial superantigens in reversal of human T lymphocyte anergy.
The induction of anergy in T lymphocytes generates T cells incapable of proliferation in response to a conventional antigenic stimulus. To investigate the induction and maintenance of anergy in human T cells, we used T cell-T cell presentation of myelin basic protein (MBP) or MBP synthetic peptides to induce anergy in vitro. Although anergic T cells responded normally to interleukin-2 (IL-2), these T cells did not produce IL-2 or IL-4 when peripheral blood mononuclear cells presented MBP or MBP peptides. Proliferation of anergic T cells was reduced by greater than 95% compared to nonanergic, control T cells. However, when autologous B cell lines were used to present MBP, anergy was partially reversed with a proliferation response about 50% of nonanergic levels. Bacterial superantigens also partially restored proliferation in anergic T cells following presentation by either B cell lines or macrophage isolated from peripheral blood mononuclear cells. Anergic, MBP-reactive T cells fully retained antigen-specific cytolytic activity against both B cell and T cell targets presenting MBP. These results suggest that T cell proliferative anergy may be reversible with both the type of antigen-presenting cell and superantigens potentially contributing to the initiation or maintenance of an autoimmune response.
Burns
J
J
Veterans Administration Medical Center, Neurovirology Research, Salt Lake City, UT 84148.
Littlefield
K
K
D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000494:pharmacology; D008222:Lymphokines / Q000096:biosynthesis; D004676:Myelin Basic Protein / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
D007376:Interleukin-2; D008222:Lymphokines; D004676:Myelin Basic Protein; D018089:Superantigens