DIFFERENCES BETWEEN T-HELPER CELL TYPE-I (TH1) AND TH2 CELL-LINES IN SIGNALING PATHWAYS FOR INDUCTION OF CONTACT-DEPENDENT T-CELL HELP

B cells get help in the antibody response by presenting antigen to helper T (T(h)) cells. Upon antigen recognition, T cells produce lymphokines that act as growth and differentiation factors for B cells, but resting B cells require additional helper signals that depend on cell contact with an activated T(h) cell. Like lymphokine secretion, contact help must be induced by antigen recognition or antigen receptor cross-linking in continuous T(h) cell lines. In the mouse, most CD4+ T cell lines can be classified into one of two stable differentiation states, T(h)1 or T(h)2, which produce different lymphokines and have different effector functions, activation requirements and cytoplasmic signalling mechanisms. This report demonstrates additional differences between T(h)1 and T(h)2 cell lines in the signalling pathways leading from the T cell antigen receptor to the induction of T(h) functions. In a system dependent on antigen presentation by B cells, B cell proliferation driven by T(h)2 cells but not T(h)1 cells was blocked by acute treatment with phorbol esters. Further experiments showed that phorbol esters blocked the induction of both contact help and lymphokine production in T(h)2 cells but not in T(h)1 cells. However, depletion of protein kinase C (PKC) activity by prolonged treatment of T cells with high concentrations of phorbol esters blocked induction of contact help and lymphokine production in T(h)1 cells but not in T(h)2 cells. These findings support the hypothesis that T(h)2 cells use a signalling pathway that is independent of PKC and that PKC activation can block this pathway. Since contact help and lymphokine secretion are affected in parallel, this difference between T(h)1 and T(h)2 cells probably reflects early events in the signalling pathway. Contact help and lymphokine production could be dissociated with cholera toxin and other cAMP agonists, but this dissociation could be explained by non-cAMP-related effects of cholera toxin on induction of contact help in T(h)2 cells, and by the direct effect of cAMP agonists on interleukin 2 gene transcription in T(h)1 cells reported by other laboratories.