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.