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(Glu60Ala30Tyr10)-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 (TDH). 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, TDH, 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.
Bibliographical noteFunding Information:
’ Supported in part by USPHS NIH Grant AI-18755 and Grant 84-22 from the Illinois Division of the American Cancer Society. * Abbreviations used: DTH, delayed-type hypersensitivity; APC, antigen-presenting cells, BSS, balanced salt solution; C, rabbit complement; CFA, complete Freund’s adjuvant; CY, cyclophosphamide; DNBS, 2,4dinitrobenzenesulfonic acid. DNFB, 2+dinitrofluorobenzene; GAT, poly (Glu60Ala’rTyr’o); LN, lymph node; MHC, major histocompatibility complex (H-2); OVA, chicken ovalbumin; Tou, effector DTH T cells; Th, T-helper cells, a, T-helper cells for DTH; TNBS, 2,4,6-trinitrobenzenesulfonic acid; TNCB, 2,4,6-trinitrochlorobenzene; TNP-SP, trinitrophenylated spleen cells; Tprlf, proliferative T cells; Ts, suppressor T cells; DMEM, Dulbecco’s modified Eagle’s medium.