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 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 T(h)2 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 T(h)2 differentiation. T-antigen-presenting cell (APC) interaction 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-modulated 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 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, T(h)2-polarizing cytokines produced upon prolonged T-APC interaction favor the T(h)2 differentiation.
Nakata
Y
Y
Division of Radiation Health, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba-city, Chiba 263-8555, Japan.
Uzawa
A
A
Suzuki
G
G
D000069594:Abatacept; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology* / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D060908:CTLA-4 Antigen; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D017635:Clonal Anergy; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D004768:Enterotoxins / Q000008:administration & dosage / Q000276:immunology; D018796:Immunoconjugates; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013211:Staphylococcus aureus / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D016207:Cytokines; D004768:Enterotoxins; D018796:Immunoconjugates; C031818:enterotoxin B, staphylococcal; D000069594:Abatacept