XENOGENEIC EFFECT .2. REQUIREMENT FOR UNACTIVATED MURINE T-CELLS DURING RESTORATION OF IMMUNE RESPONSIVENESS WITH XENOGENEIC RECONSTITUTION FACTOR

Abstract

Studies were conducted on the mechanism of action of a soluble mediator which was generated in human mixed lymphocyte cultures and assayed for helper activity in T [thymus-derived] cell deficient murine spleen cell cultures. The mediator, termed xenogeneic reconstitition factor of XRF, restored the anti-sheep erythrocyte plaque-forming cell response of spleen cells from thymectomized, lethally irradiated and syngeneic bone marrow transplanted (TxB) mice. To obtain a maximal antibody response, the XRF had to be present sometime during the first 24-40 h of the induction process. XRF was also required during the last 24 h of the incubation period. A striking synergistic effect was obtained by combined exposure of the T cell deficient spleen cell cultures to XRF during the 1st and last days of culture. This suggested a bi-modal mechanism of action of XRF, and the possibility that in addition to providing a signal to the B [bone marrow-derived] cells, XRF-mediated activation of the residual TxB splenic T cells was crucial to the successful restoration of the antibody response. Treatment of the nonadherent splenocytes from the TxB mice with anti-T cell serum and guinea pig complement completely abrogated the antibody response of these cells in the presence of adherent spleen cells, sheep erythrocytes and XRF. The antibody response of this combination of cells, antigen and XRF and reconstituted by a population of unimmunized murine T cells which, in the absence of XRF, were totally unable to restore responsiveness. B cell activation for the formation of antibody probably involves the mandatory co-participation of 2 functionally distinct helper activities.