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.

The differential role of CD86 and CD80 co-stimulatory molecules in the induction and the effector phases of contact hypersensitivity.

Contact hypersensitivity (CH) has served as a useful model for investigating the allergen-specific immune responses of T cells and skin-associated antigen-presenting cells. We examined the distinct role between CD80 and CD86 on hapten-induced CH in both an induction and an effector phase. Intraperitoneal injection of mAb against CD86, but not CD80, 2 h before sensitization with epicutaneous application of dinitrofluorobenzene led to an almost complete inhibition of ear swelling, and histologically a marked reduction of edema, inflammatory polymorphonuclear cells and lymphocyte infiltration in the dermis.

Preferential dependence of autoantibody production in murine lupus on CD86 costimulatory molecule.

Blockade of the interactions between CD28/CTLA-4 and their ligands, CD80 (B7, B7.1)/CD86 (B70, B7.2), seems an attractive means to induce antigen-specific peripheral tolerance in organ transplantation and autoimmune disease.