Active role of T cells in promoting an in vitro autoantibody response to self erythrocytes in NZB mice.

The in vitro anti-self erythrocyte antibody response of NZB spleen cells appears to be influenced directly by T cells. Thy-1+, L3T4+ helper T cells are required for: (i) the generation in vitro of MRBC-specific IgM and IgG AFC by spleen cells from 'autoimmune' (9-12-month old) NZB mice and (ii) the generation in vitro of MRBC-specific IgM and IgG AFC by spleen cells depleted of suppressor cells from pre-autoimmune (2-3-months-old) NZB mice which show no clinical signs of an anti-MRBC response. It is evident from the present and previous studies that the anti-MRBC autoantibody response is regulated in pre-autoimmune spleen cell populations by Ly2+ T cells. Ly2-T cells from both pre-autoimmune and autoimmune mice in sufficient numbers can overcome this normal regulation and promote the anti-MRBC response in cultures of unfractionated pre-autoimmune spleen cells. Ly2- T cells isolated from autoimmune NZB mice were consistently more active in this than the Ly2- T cells isolated from pre-autoimmune mice, suggesting an enrichment of MRBC-reactive Ly2- T cells in autoimmune NZB mice. The Ly2- T cells from autoimmune NZB mice greatly enhance the autoimmune anti-MRBC response relative to a modest enhancement of the response to a foreign antigen, SRBC, produced by the same cells. These data indicate that T cells play an important role both in supporting the autoantibody response to MRBC and in disrupting tolerance, leading to autoimmunity in NZB mice.