In vivo staphylococcal enterotoxin B (SEB)-primed murine splenocytes secrete mediators which suppress CD25(hi) expression and cell cycle progression of naive splenocytes in response to SEB in vitro.
Administration of bacterial superantigen results in clonal activation of T cells followed by a state of hyporesponsiveness to subsequent antigen stimulation. Using a coculture system, we showed that the splenocytes from staphylococcal enterotoxin B (SEB)-injected BALB/c mice suppressed the proliferative response of naive splenocytes to SEB stimulation. The suppressive effect also occurred in Fas-deficient MRL-lpr/lpr mice. When naive responder cells were separated by a semipermeable membrane from SEB-primed effector cells, the suppressive effect remained apparent. The hyporesponsiveness of responder cells did not result from excessive induction of apoptosis, but rather from prevention of entering the S and G2/M phases of the cell cycle. The IL-2 levels in culture supernatants were low with the presence of SEB-primed effector cells. However, addition of IL-2 to the cocultures only partially reversed the inhibitory effect. Further studies revealed a reduced level of the CD25(hi) subpopulation in responder cells when cultured in the transwell with the presence of SEB-primed effector cells compared to that with saline-primed controls. This inhibitory effect was not observed for SEB-induced activation of CD25(int) and CD69 expression. Taken together, using a transwell culture system, we show in this study an inhibition of CD25(hi) expression and cell cycle arrest in target cells, which may serve at least in part the mechanisms of SEB-induced hyporesponsiveness.
Hsu
L J
LJ
Department of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan, Taiwan, Republic of China.
Jan
M S
MS
Lin
Y S
YS
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D017209:Apoptosis; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004768:Enterotoxins / Q000008:administration & dosage / Q000276:immunology*; D053222:Fas Ligand Protein; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000276:immunology*; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology; D037181:Lectins, C-Type; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000008:administration & dosage / Q000276:immunology*; D019014:fas Receptor / Q000235:genetics / Q000276:immunology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D004768:Enterotoxins; D053222:Fas Ligand Protein; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D018089:Superantigens; D019014:fas Receptor; D000099192:CD69 Antigens; C505658:Fasl protein, mouse; C031818:enterotoxin B, staphylococcal