REGULATION OF THE INTERACTION BETWEEN TH1 AND TH2 T-CELL CLONES TO PROVIDE HELP FOR ANTIBODY-PRODUCTION IN-VIVO

On the premise that an individual with an intact immune system has the capability to develop both cellular and antibody immune responses sup ported by the balance between the lymphokines secreted by Thelper (Th) cells, we studied the interaction between different types of Th cell clones in vivo and the parameters that may affect this interaction. We used an adoptive transfer system in which nude or lethally irradiated mice were reconstituted with histocompatible CD4(+) keyhole limpet he mocyanin (KLH)-specific T cell clones with defined lymphokine profiles . This approach allowed us to study the effects of the cognate interac tion between T and B cells in the presence of a defined set of lymphok ines. We demonstrated that the co-transfer of both subsets of Th cells resulted in increased production of IgA, and decreased production of IgE and IgG2a. The concomitant presence of both cell types also increa ses their functional survival in vivo. We have shown that in the prese nce of a Th2 clone, higher immunization doses (above 100 mu g trinitro phenol (TNP)-KLH/mouse) result in increased production of IgE and IgG1 . In contrast, when a Th1 clone is present, low immunization doses (le ss than 50 mu g TNP-KLH/mouse) resulted in increased production of IgG 2a. We were also able to show that the neutralization of interleukin-4 (IL-4) and or interferon-gamma (IFN-gamma) was sufficient to abrogate most of the regulatory effects caused by the Th2 or the Th1 clone res pectively. Our results indicate that the subset of T cell(s) transferr ed determines the type of response obtained. In addition, the data pre sented indicate that the antigen dose used for immunization can modula te the quantitative parameters of the response. Furthermore, we have s hown that the interaction between the two subsets of T cells in vivo i s characterized by both antagonistic and agonistic effects and that mo st of the regulatory effects exerted by one subset over the other are mediated by IL-4 or IFN-gamma.