Infection breaks T-cell tolerance

Nature. 1992 Sep 3;359(6390):79-82. doi: 10.1038/359079a0.


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.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / physiology*
  • Enterotoxins
  • Immune Tolerance*
  • Interleukins / physiology
  • Mice
  • Mice, Inbred BALB C
  • Nematode Infections / immunology*
  • Nippostrongylus*
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*


  • Enterotoxins
  • Interleukins
  • Receptors, Antigen, T-Cell, alpha-beta
  • enterotoxin B, staphylococcal