The Journal of Immunology, Vol 154, Issue 12 6306-6313, Copyright © 1995 by American Association of Immunologists

ARTICLES

Superantigen-induced anergy in cytotoxic CD8+ T cells

A Sundstedt, I Hoiden, J Hansson, G Hedlund, T Kalland and M Dohlsten
Pharmacia Oncology Immunology, Lund, Sweden.

This study describes the use of bacterial superantigens to investigate the mechanisms governing peripheral tolerance in CD8+ T cells. Administration of superantigens to mice activates T cells to proliferation, cytokine production, and cytotoxicity, but responding cells subsequently enter a state of hyporesponsiveness or are deleted. Superantigen-induced inactivation has so far mainly been demonstrated for CD4+ T cells. Injection of amounts of the superantigen staphylococcal enterotoxin A (SEA) that are optimal for T cell activation and which induce anergy in CD4+ T cells result in preserved responsiveness in CD8+ CTLs. In contrast, we found that intravenous injection of low concentrations of SEA induced a profound down- regulation of the cytotoxic function in SEA-reactive CD8+ TCR V beta 11+ T cells. No reduction in the number of CD8+V beta 11+ T cells was found, suggesting that anergy and not deletion is the main mechanism for the observed cytotoxic hyporesponsiveness. The cytotoxic anergy was evident 2 days after low-dose priming and remained present 4 wk later, indicating a rapid induction phase and long-lasting persistence. The anergized CD8+ T cell subset expressed lower levels of the alpha- (CD11a) chain of the cell adhesion molecule lymphocyte function- associated Ag 1 (LFA-1) and failed to mediate cytotoxicity, but retained the capacity to proliferate, express IL-2R, produce IFN-gamma, and express granzyme mRNA, which imply a partial defect in TCR- transduced signals. Taken together, these findings suggest that there is a biphasic stimulus-dependent threshold for acquiring responsiveness or anergy in CD8+ T cells.

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