Infection breaks T-cell tolerance

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Abstract
CLONAL deletion or clonal anergy establish tolerance in T cells that bear potentially autoreactive antigen receptors1–15. Here we report that concomitant infection with the nematode Nippostron-gylus brasiliensis breaks an established T-cell tolerance induced by injection of mice with Staphylococcus enterotoxin B (SEB)16,17. CD4+ T cells from SEB-tolerant mice did not produce either interleukin-2 or interleukin-4 when challenged in vitro with SEB. N. brasiliensis infection of SEB-primed animals resulted in a normal expansion of SEB-tolerant CD4+Vβ8+ T cells in vivo as well as an equivalent increase of SEB-reactive, interleukin-4-producing CD4+Vβ8+ T cells both in SEB-tolerant and in normal animals. Thus, infection with N. brasiliensis circumvented the tolerance established with SEB. Activation of anergic, potentially autoreactive CD4+ T cells by infectious agents seems to be a major pathway for the initiation of autoimmune diseases15. Our results suggest that infectious agents may break tolerance in potentially autoreactive CD4+ T cells by activation of alternative reaction pathways.