Persisting T cells in rats tolerant of human serum albumin. The significance of tolerant and nonimmune T cells which preferentially restrict high affinity antibody synthesis.

Abstract

The adoptive response of primed rat thoracic duct lymphocytes ('TDL) following specific antigen challenge (soluble human serum albumin, s-HSA) was restricted when cells were transferred into syngeneic, adult (AS2 X AS)F1 hybrid recipients in comparison with irradiated hosts. This adoptive memory response was also inhibited in irradiated recipients by transferring nonimmune TDL along with 'TDL. Recirculating B cells (B-TDL) did not inhibit the 'TDL response, indicating that the adoptive secondary response was regulated by T cells. Antibody synthesis was preferentially restricted in the high affinity memory cell precursor population, demonstrating a role for T cells in regulating the maturation of antibody affinity. The adoptive memory response was liberated from this T regulatory effect in adult recipients when hosts were challenged with the alum-precipitated adjuvant form (HSA-adj) rather than the soluble form of HSA. Since the adoptive memory response was sensitive to the presence or absence of T cells, this experimental model was used to determine whether or not T cells were eliminated from HSA-tolerant rats. Antibody synthesis by 'TDL was reduced approximately 10-fold compared with controls when transferred into tolerant recipients and challenged with either s-HSA or HSA-adj; a similar reduction was not observed by substituting bovine serum albumin (BSA) 'TDL and challenging with s-BSA. The tolerance-induced inhibition of HSA 'TDL was destroyed by irradiation and TDL from HSA-tolerant donors were more effective than normal nonimmune TDL in reducing the adoptive HSA 'TDL response. HSA-tolerant TDL did not inhibit the BSA 'TDL response significantly. The results indicate that T cells are not eliminated by tolerance induction in this model and after interaction with tolerogen may exert an active (or competitive) role in restricting antibody synthesis by high affinity B memory cell precursors. However, the fact that tolerant T cells are not able to prevent a primary response suggests that unresponsiveness to HSA in the T compartment represents a functional deficiency and not an active suppression at this level. Nevertheless, the presence of these tolerant cells probably accounts for the failure of antibody affinity to mature in partially tolerant rats.