In vivo induction of anergy in peripheral V beta 8+ T cells by staphylococcal enterotoxin B.
We have developed a model of peripheral in vivo T cell tolerance that is induced by administration of the protein superantigen staphylococcal enterotoxin B (SEB). Rather than activating V beta 8+ T cells, in vivo administration of SEB induced in them a profound state of anergy. This was shown by their failure to proliferate to subsequent in vitro restimulation with SEB or to anti-V beta 8 antibodies. This unresponsiveness was V beta 8 specific since T cells from SEB-immunized mice responded normally to other antigens. 8 d after SEB administration, there was no reduction in the number of V beta 8+ T cells or in the intensity of V beta 8 T cell receptor (TCR) expression. Although a portion of the V beta 8+ T cells from SEB-primed mice were able to express interleukin 2 receptors (IL-2Rs), they failed to proliferate in response to exogenous IL-2, indicating they were defective in their IL-2 responsiveness. 2-4 wk after SEB administration, there was a reduction of approximately 50% in the number of V beta 8+ cells in immunized compared with control animals. There was, however, no reduction in the level of TCR expression on the remaining V beta 8+ cells. These data demonstrate that proteins that activate T cells in vitro in a V beta-specific manner can induce a state of anergy in peripheral T cells in vivo and may possibly further mediate clonal deletion in a portion of the tolerized cells.
Rellahan
B L
BL
Division of Cytokine Biology, Food and Drug Administration, National Institutes of Health, Bethesda, Maryland 20892.
Jones
L A
LA
Kruisbeek
A M
AM
Fry
A M
AM
Matis
L A
LA
D000818:Animals; D004768:Enterotoxins / Q000276:immunology / Q000494:pharmacology*; D007108:Immune Tolerance; D007114:Immunization; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013211:Staphylococcus aureus; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D004768:Enterotoxins; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; C031818:enterotoxin B, staphylococcal