Control of CD4 T cell fate by antigen re-stimulation with or without CTLA-4 engagement 24 h after priming

After two consecutive inoculations with Staphylococcus enterotoxin B (SEB) at 24 h intervals in vivo, CD4 T cells became anergic to the antigen challe nge in vitro, Administration of anti-CTLA-4 mAb in conjunction with the sec ond SEE inoculation 24 h after antigen priming interfered with anergy and C D4 T cells became T(h)2 cells. However, the anergy induction was not ablate d when SEE and anti-CTLA-4 mAb were administered 48 or 72 h after antigen p riming. Moreover, anti-CTLA-4 mAb without SEE did not interfere with anergy nor promoted the T(h)2 differentiation. T-antigen-presenting cell (APC) in teraction in vitro in the presence of high doses of antigen and anti-CTLA-4 mAb induced a T(h)2-polarizing cytokine IL-6 and IL-10, IL-10 then down-mo dulated a T(h)1-polarizing cytokine IL-12, The results demonstrate that 24 h after the initial antigen stimulation, CD4 T cells enter the critical act ivation phase where antigen re-stimulation with or without CTLA-4 engagemen t alters the fate of the cell, anergy or differentiation respectively. Once anergy is interfered with, T(h)2-polarizing cytokines produced upon prolon ged T-APC interaction favor the Th2 differentiation.