T cells with T cell receptor (TCR) transgenes that recognized CD1 on syngeneic B cells stimulated B cells to secrete immunoglobulins in vitro. The CD4⁺, CD8⁺, or CD4⁻CD8⁻ T cells from the spleen of the TCR transgenic BALB/c donors induced lupus with anti–double stranded DNA antibodies, proteinuria, and immune complex glomerulonephritis in irradiated BALB/c nude mice reconstituted with nude bone marrow. Injection of purified CD4⁻CD8⁻ T cells from the marrow of transgenic donors prevented the induction of lupus by the transgenic T cells. Transgenic T cells that induced lupus secreted large amounts of interferon (IFN)-γ and little interleukin (IL)-4, and those that prevented lupus secreted large amounts of IL-4 and little IFN-γ or IL-10.