Infection breaks T-cell tolerance.
Clonal deletion or clonal anergy establish tolerance in T cells that bear potentially autoreactive antigen receptors. Here we report that concomitant infection with the nematode Nippostrongylus brasiliensis breaks an established T-cell tolerance induced by injection of mice with Staphylococcus enterotoxin B (SEB). 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+V beta 8+ T cells in vivo as well as an equivalent increase of SEB-reactive, interleukin-4-producing CD4+V beta 8+ 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 diseases. Our results suggest that infectious agents may break tolerance in potentially autoreactive CD4+ T cells by activation of alternative reaction pathways.
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
M
M
Röcken
J F
JF
Urban
E M
EM
Shevach
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D004768:Enterotoxins; D007108:Immune Tolerance; D007378:Interleukins / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009349:Nematode Infections / Q000276:immunology*; D009559:Nippostrongylus; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*
D004768:Enterotoxins; D007378:Interleukins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C031818:enterotoxin B, staphylococcal