In vivo effects of GK1.5 (anti-L3T4a) monoclonal antibody on induction and expression of delayed-type hypersensitivity

Abstract

The in vivo effects of monoclonal GK1.5 antibody, directed against the L3T4a determinant expressed on Class II-restricted T cells, on the induction and expression of murine delayedtype hypersensitivity (DTH) responses were examined. Development and expression of both hapten (2,4-dinitrofluorobenzene and 2,4,6-trinitrochlorobenzene)- and protein antigen poly(Glu 60Ala 30Tyr 10)-specinc DTH are significantly inhibited by injection of monoclonal anti-L3T4a antibody. The inhibitory effects of anti-L3T4a were most pronounced when administered during the afferent (induction) phase of the DTH response, leading to the functional inhibition of the generation of both polyclonal lymph node T-proliferative cells (Tprlf) and DTH effector cells (T DH). The in vivo inhibitory effect is apparently unrelated to preferential induction of suppressor T cells as GK1.5 inhibited DTH induction in cyclophosphamide-treated as well as normal recipients. L3T4a expression on the various T-cell subsets involved in DTH induction and elicitation was also examined. The data show that three functionally distinct, antigenspecific T-cell subsets, Tprlf, T DH, and Th cells involved in DTH induction, bear the Lyt 1 +2 −, L3T4 + phenotype. Possible mechanisms where in vivo injection of anti-L3T4a inhibits Class II-restricted T-cell subsets involved in DTH induction and expression, including immune depletion and inhibition of T-cell-receptor/ligand interactions, are discussed.