THE ROLE OF T-HELPER LYMPHOCYTES IN PRIMING FOR EXPERIMENTAL AUTOIMMUNE GLOMERULONEPHRITIS IN THE BN RAT

In our model of experimental autoimmune glomerulonephritis (EAG), BN rats given a single IM injection of homologous glomerular basement membrane (GBM) in FCA develop anti-GBM autoantibodies with focal glomerulonephritis. To investigate the role of lymphocytes in the induction of EAG, we examined the effects of antigen rechallenge and of adoptive cell transfer from donors with nephritis to naive recipients. Groups of animals were rechallenged with GBM in FCA following either low (non-nephritogenic) doses of GBM, or following resolution of EAG. This resulted in an enhanced anti-GBM antibody response in both groups, suggesting the presence of GBM specific T or B memory cells. To investigate this possibility, spleen cells from animals with EAG were transferred into lightly irradiated recipients. There was no significant rise in anti-GBM antibody levels after transfer. However, subsequent challenge with GBM in FCA resulted in an enhanced anti-GBM antibody response by 2 weeks when compared with recipients of normal spleen cells. Cells capable of priming for EAG developed by week 4 after immunization of donors and persisted in the recipients for at least 24 weeks. To investigate which cel type was responsible for this effect, we depleted or positively selected donor spleen cells prior to transfer, using Dynabeads coated with monoclonal antibodies to Th or B lymphocytes. Depletion of Th cells, but not B cells, reduced the enhanced anti-GBM antibody response of recipients challenged with GBM in FCA. Positively selected Th cells, but not B cells, resulted in an enhanced anti-GBM antibody response similar to that in positive controls. These results demonstrate the presence of immunological memory for the autoantigen and show that priming for EAG is mediated by Th lymphocytes. © 1993 Academic Press, Inc.