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International Immunology, Vol. 12, No. 4, 459-466, April 2000
© 2000 Japanese Society for Immunology

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

Yukiko Nakata, Akiko Uzawa and Gen Suzuki

Division of Radiation Health, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba-city, Chiba 263-8555, Japan

Correspondence to: G. Suzuki

After two consecutive inoculations with Staphylococcus enterotoxin B (SEB) at 24 h intervals in vivo, CD4 T cells became anergic to the antigen challenge in vitro. Administration of anti-CTLA-4 mAb in conjunction with the second SEB inoculation 24 h after antigen priming interfered with anergy and CD4 T cells became Th2 cells. However, the anergy induction was not ablated when SEB and anti-CTLA-4 mAb were administered 48 or 72 h after antigen priming. Moreover, anti-CTLA-4 mAb without SEB did not interfere with anergy nor promoted the Th2 differentiation. T–antigen-presenting cell (APC) interaction in vitro in the presence of high doses of antigen and anti-CTLA-4 mAb induced a Th2-polarizing cytokine IL-6 and IL-10. IL-10 then down-modulated a Th1-polarizing cytokine IL-12. The results demonstrate that 24 h after the initial antigen stimulation, CD4 T cells enter the critical activation phase where antigen re-stimulation with or without CTLA-4 engagement alters the fate of the cell, anergy or differentiation respectively. Once anergy is interfered with, Th2-polarizing cytokines produced upon prolonged T–APC interaction favor the Th2 differentiation.

Keywords: anergy, IL-6, IL-10, Staphylococcus enterotoxin B, Th2

Transmitting editor: M. Taniguchi


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