Critical contribution of CD80 and CD86 to induction of anterior chamber-associated immune deviation.
Intraocular inoculation of antigens induces anterior chamber-associated immune deviation (ACAID), which is mediated by development of regulatory T cells in response to antigen-presenting cells (APC) pre-conditioned by intraocular transforming growth factor-beta (TGF-beta). In this study, we examined the involvement of T-cell co-stimulatory molecules in this process. To mimic the intraocular APC, thioglycollate-elicited peritoneal exudate cells (PEC) were pre-treated with TGF-beta in vitro. Expression of CD80, CD86, OX40 ligand (OX40L) and CD70 was analyzed by flow cytometry. Contribution of these molecules to co-stimulatory activity of TGF-beta-treated PEC on antigen-stimulated T-cell proliferation and cytokine production was determined by inhibition with blocking antibodies in vitro. Contribution of CD80 and CD86 to induction of ACAID was determined by the administration of blocking antibodies at intraocular antigen inoculation in vivo. TGF-beta-treated PEC expressed CD80 and CD86 but not OX40L or CD70. Antigen-stimulated T cells proliferated and produced IL-10, but not IFN-gamma, in response to co-stimulation by TGF-beta-treated PEC, which was abrogated by blocking antibodies against CD80 and CD86. Induction of regulatory cells mediating ACAID was abolished by in vivo blockade of CD80 and CD86. The present results indicated that CD80 and CD86 play a critical role in induction of ACAID, possibly by co-stimulating expansion and IL-10 production of regulatory T cells in response to TGF-beta-conditioned APC.
Tsukahara
Rintaro
R
Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. rintaro@tokyo-med.ac.jp
Takeuchi
Masaru
M
Akiba
Hisaya
H
Kezuka
Takeshi
T
Takeda
Kazuyoshi
K
Usui
Yoshihiko
Y
Usui
Masahiko
M
Yagita
Hideo
H
Okumura
Ko
K
D000818:Animals; D000867:Anterior Chamber / Q000276:immunology*; D000906:Antibodies; D018122:B7-1 Antigen / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D005122:Exudates and Transudates / Q000166:cytology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010537:Peritoneum / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D000906:Antibodies; D018122:B7-1 Antigen; D016212:Transforming Growth Factor beta; D010047:Ovalbumin