Reduced contact sensitivity reactions in mice treated with monoclonal antibodies to leukocyte function-associated molecule-1 and intercellular adhesion molecule-1

Abstract

We have investigated the effect of the administration of mAb against leukocyte function-associated molecule-1 (CD11a/CD18) and intercellular adhesion molecule-1 (CD54) on the delayed-type hypersensitivity reaction in 2,4-dinitro-1-fluorobenzene-sensitized CD2F1 mice. An i.p. injection of the mAb FD441.8 against CD11a at the time of ear challenge led to an almost complete inhibition of ear swelling compared with control animals. Administration of anti-CD54 mAb, 3E2 or YN1/1.7.4, before challenge, resulted in approximately 50% reduction of the delayed-type hypersensitivity response. The decrease in ear swelling reflected a profound inhibition of the edema and the cell infiltration in ears from animals treated with anti-CD11a, and a partial inhibition with anti-CD54 treatment. In addition, the threefold increase in the number of cells recovered from the draining lymph nodes 24 h after challenge in sensitized mice injected with normal IgG was ablated in mice treated with anti-CD11a and partially reduced in anti-CD54-treated animals. Immunohistochemistry and flow cytometry analysis demonstrated that the in vivo administered anti-CD11a mAb was associated with the surface of the majority of the cells in the lymph nodes 24 h after injection and challenge, whereas the anti-intercellular adhesion molecule-1 mAb reacted preferentially with the vascular endothelium. It is concluded that leukocyte function-associated molecule-1 and intercellular adhesion molecule-1 contribute to the generation of an optimal delayed-type hypersensitivity response.