Activation-induced cell death signalling in CD4+ T cells by staphylococcal enterotoxin A

Abstract

Staphylococcal enterotoxin A (SEA) is a potent stimulator of CD4+ and CD8+ T cells, the immunotoxic action of which remains unclear. We investigated the in vitro effects of SEA on freshly isolated human peripheral blood lymphocytes depleted of CD8+ T cells. Proliferation and flow cytometry analysis indicated that SEA generated an activation-induced cell death (AICD) phenomenon that was characterized by an increased expression of the chemokine receptor CCR5 on the CD4+/CD45RO+ T cell subset. Incubation of cells with glycoprotein secretion inhibitor monensin A completely blocked cell proliferation, affecting mainly the CD4+/CD45RO+ T cell subset. The IL-2 mRNA levels were increased just hours after SEA stimulation, accompanied by an increase in the expression of CD25, indicating a possible involvement of IL-2 in the AICD process. We observed a 15-fold mRNA reduction of the transcription factor Yin Yang 1 (YY1) at the proliferation peak, and an increase of the receptors CCR5, CD95 and DR5 on the CD45RO+/CD4+ T cell subset. These findings suggest that SEA triggers a TCR-mediated AICD mechanism in CD4+ T cells, the intracellular signalling of which is probably modulated, at least, by YY1.