Tubular antigen-derivatized cells induce a disease-protective, antigen-specific, and idiotype-specific suppressor T cell network restricted by I-J and Igh-V in mice with experimental interstitial nephritis.

Abstract

The nephritogenic effector T cell response producing interstitial nephritis in mice can be largely inhibited by the adoptive transfer of suppressor T cells before or after the induction of disease. These suppressor T cells are harvested from donor mice primed with tubular antigen-derivatized syngeneic lymphocytes, and two subsets of suppressor cells can be characterized within this donor cell population. The first suppressor cell in this network is an L3T4+, I-J+, RE-Id+ cell (Ts-1). Ts-1 cells are antigen-binding suppressor cells that inhibit afferent phase immune responses and, in the presence of tubular antigen, specifically induce Lyt-2+, I-J+ cells (Ts-2) that are antiidiotypic (RE-Id-binding) suppressors. The Ts-2 cell is functionally restricted in its suppressive effect by I-J and Igh-V gene products, and acts on the effector limb of the cell-mediated anti-tubular basement membrane immune response. These studies provide an experimental basis for further efforts to use immunoregulatory modulation in the control of autoimmune renal disease.