Reversal of T‐Cell Anergy in Autoimmune (NZB X NZW)F1 Mice by Transfer with Non‐Antigen Specific CD4+ T Cells from Young, Syngeneic Donors

Abstract

The F1 hybrid of NZB and NZW mice is a well-known model of systemic lupus erythematosus characterized by B-cell hyperactivity, production of autoantibodies and immune-complex formation. These phenomena have been regarded as pathogenetic for the development of glomerulonephritis and early death in renal failure. It has been previously reported that aged and overt diseased NZB/W mice also display impaired T-cell responses. In the present report we demonstrate an age-dependent decline in the capacity of NZB/W mice to mount in vivo cutaneous delayed type hypersensitivity (DTH) and antibody responses to a hapten, oxazolone (OXA). Moreover, in vitro proliferative response to Concanavalin A (Con A) and production of interleukin 2 (IL-2) were severely depressed in aged NZB/W mice. In transfer experiments we show that a single i.p. injection of non-immune mononuclear spleen cells from young NZB/W mice to old diseased syngeneic recipients restores DTH reactivity and increases the antibody response to OXA. This effect is a CD4(+)-dependent process since the restoration of T-cell responses was abrogated upon elimination of CD4+ donor T cells. Overall, our results indicate that limited numbers of CD4+ T cells display substantial immunoregulatory properties reversing the state of anergy in autoimmune NZB/W mice.