Activation-induced cell death signalling in CD4+ T cells by staphylococcal enterotoxin A.
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.
Department of Applied Biochemistry and Immunology, Institute of Molecular Biology and Biotechnology, Vassilika Vouton, Heraklion, Crete, Greece.
Filippos
F
Porichis
Antigoni
A
Morou
Stavroula
S
Baritaki
Demetrios A
DA
Spandidos
Elias
E
Krambovitis
D017209:Apoptosis / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004768:Enterotoxins / Q000633:toxicity*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation / Q000187:drug effects*; D008985:Monensin / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D019713:Receptors, CCR5 / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
D004768:Enterotoxins; D018836:Inflammation Mediators; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger; D019713:Receptors, CCR5; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; D019014:fas Receptor; C026066:enterotoxin A, Staphylococcal; D008985:Monensin; D017493:Leukocyte Common Antigens