Cytokine deviation induced by intrathymic injection of staphylococcal enterotoxin B (SEB).
We have previously shown that intrathymic (i.t.) injection of staphylococcal enterotoxin B (SEB) to mice induces both T cell clonal deletion and IL-2-dependent anergy. In the present study, we have used a quantitative RT-PCR to demonstrate that i.t. administration of SEB induced a significant decrease in the levels of the IL-2 and IFN-gamma mRNAs in total splenocytes, from day 7 to day 28 post-injection. I.t. SEB injection also induced a significant increase in the levels both of IL-10 and TGF-beta mRNAs on day 7, leading to a significant enhance in the IL-10 + TGF-beta/IL-2 + IFN-gamma mRNA ratio on days 7 and 28. By contrast, IL-10 and TGF-beta mRNAs were unchanged after intraperitoneal (i.p.) or subcutaneous (s.c.) SEB injections, although both IL-2 and IFN-gamma mRNA levels were decreased. The cytokine mRNA ratio was enhanced on days 7 and 28 after i.p. injection. Interestingly, a cytokine mRNA ratio of a least 10 in favour of IL-10 plus TGF-beta mRNAs was correlated with the hyporesponsive state observed in vitro after i.t. and i.p. injections. Our results clearly demonstrate that i.t. SEB administration induces a switch from Th1-type to Th2-type cytokine expression in the spleen. The deviation from IL-2 plus IFN-gamma towards IL-10 plus TGF-beta expression could be responsible for the immunoregulatory effect exerted upon SEB-reactive T cells, which is characterized by an IL-2-dependent, specific anergy in vitro. Moreover, it highlights the crucial role of the route of SEB injection in the pattern of cytokine expression.
Goettelfinger
P
P
Laboratoire de Physiologie Thymique, Centre Chirurgical Marie-Lannelongue, Université Paris-Sud, 133, avenue de la Résistance, 92350 Le Plessis-Robinson, France.
Lecerf
F
F
Berrih-Aknin
S
S
German-Fattal
M
M
D000818:Animals; D017635:Clonal Anergy / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004768:Enterotoxins / Q000008:administration & dosage*; D005260:Female; D007272:Injections, Intralymphatic; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000819:agonists* / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D004768:Enterotoxins; D007376:Interleukin-2; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma