The regulation of autoantibody production in Heymann's nephritis by T lymphocyte subsets

The role of T lymphocyte subsets in the regulation of the autoantibody response to renal tubular antigen and the development of Heymann's nephritis (HN) in different rat strains was investigated in the present study. WF rats were highly susceptible to HN induction, PVG rats were moderately susceptible, whereas DA and BN were resistant. The induction of an autoantibody response to renal tubular antigen and HN in PVG rats was T cell-dependent as they were abrogated by neonatal thymectomy and T cell depletion after adult thymectomy, whole body irradiation and bone marrow reconstitution. Reconstitution of neonatal thymectomized and adult thymectomized whole body irradiated and bone marrow reconstitution of PVG rats with different T lymphocyte subsets revealed that the induction of an autoantibody response to renal tubular antigen in these animals required help from a long lived, W3/25+ T cell subset and was down regulated by a MRC OX8+ T cell subset. Adoptive transfer experiments demonstrated that the suppressor T cells involved were short lived and were probably generated by the interaction between a W3/25+ inducer and a MRC OX8+ precursor subpopulation. The suppressor precursor T cells were recently derived from the thymus as the suppressor T cell response was abrogated by adult thymectomy, an effect which could only be fully restored by thymic grafting or injection of adult thymocytes but not by the injection of normal spleen or lymph node cells. As adult thymectomy had less effect on the autoantibody response and HN development in the highly susceptible WF rats, the difference in disease susceptibility between the WF and PVG rats may be the result of different suppressor T cell recruitment from the adult thymus. Since adult thymectomy did not affect disease development in the DA and BN rats, the recently thymus-derived suppressor T cells did not contribute to innate disease resistance in these rat strains.