Injection of mouse thyroglobulin and/or adult thymectomy do not break tolerance to thyroglobulin during the lupus like graft versus host disease in mice

In a previous paper (Gleichmann, van Elven & van der Veen, 1982), it had been reported that, in contrast to lupus like autoantibodies such as anti-DNA, autoantibodies to mouse thyroglobulin (MTg) were not detectable in serum of F₁ mice suffering from a lupus like graft versus host disease (GVHD) (GVH F₁). In the present paper, possible explanations for this restricted autoantibody formation during the potent allogeneic stimulation were investigated. The main question was whether the natural level of circulating MTg was too low to induce the formation of anti-MTg antibodies in GVH F₁ mice. Existence, in the F₁ mice studied, of B cells capable of producing anti-MTg antibodies was demonstrated by injection of lipopolysaccharide (LPS) and exogeneous MTg. However, MTg injected into various F₁ mice at the onset of the GVH reaction (GVHR) failed to overcome the lack of antibody formation to MTg even though the GVHR led to a severe lupus like disease. Furthermore, adult thymectomy (ATx) of either the recipients, the donors, or both also did not break tolerance to MTg during the GVHR, irrespective of administration of exogeneous MTg. Thus, neither intravenous injection of MTg nor ATx, designed to remove T suppressor (Ts) cells, is adequate to enable an autoantibody response to MTg during lupus like GVHD. Hence, the non-specific T cell help that causes lupus like GVHD seems to be intrinsically insufficient to trigger the Tg reactive B cells. We suggest that globular proteins, such as Tg, require specific T cell help. In the presence of only non-specific T help, self-antigens such as DNA seem to be more apt than globular proteins to provide an effective signal 1 to the corresponding autoreactive B cells.