The role of CTLA-4 in murine contact hypersensitivity.
CTLA-4 (CD152) shares its ligand with a costimulatory molecule, CD28, and functions as a negative regulator in T cell activation. We examined the role of CTLA-4 in both induction and effector phases of contact hypersensitivity induced by using two allergens. Treatment with anti-CTLA-4 monoclonal antibody at sensitization, but not at challenge, significantly enhanced Th1- and Th2-dominant contact hypersensitivity reactions elicited by dinitrofluorobenzene and fluorescein isothiocyanate, respectively. CTLA-4 was faintly expressed on regional lymph node T cells even in naïve mice, and its transcription determined by reverse transcriptase polymerase chain reaction was clearly enhanced at 72 h after sensitization. Treatment with anti-CTLA-4 monoclonal antibody at sensitization significantly augmented the total cell number in regional lymph nodes and proliferative responses of T cells against specific haptens. This higher sensitivity in lymph node T cells against specific haptens was maintained over the month after treatment. Our results suggest that CTLA-4 on T cells may regulate the induction of antigen-specific T cells in the regional lymph nodes in allergic contact dermatitis.
Nuriya
S
S
Department of Immunology, National Children's Medical Research Center, Tokyo, Japan.
Enomoto
S
S
Azuma
M
M
D000069594:Abatacept; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D060908:CTLA-4 Antigen; D003877:Dermatitis, Contact / Q000276:immunology / Q000503:physiopathology*; D004139:Dinitrofluorobenzene / Q000276:immunology; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D018796:Immunoconjugates; D008198:Lymph Nodes / Q000187:drug effects / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000502:physiology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D000069594:Abatacept; D004139:Dinitrofluorobenzene; D016650:Fluorescein-5-isothiocyanate