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.