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.
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.
Neilson
E G
EG
McCafferty
E
E
Mann
R
R
Michaud
L
L
Clayman
M
M
D000818:Animals; D000941:Antigens / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001485:Basement Membrane / Q000276:immunology; D005802:Genes, MHC Class II; D006183:H-2 Antigens / Q000235:genetics; D006649:Histocompatibility Antigens / Q000235:genetics; D006968:Hypersensitivity, Delayed; D007116:Immunization, Passive; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D007684:Kidney Tubules / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D009395:Nephritis, Interstitial / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000941:Antigens; D001324:Autoantigens; D006183:H-2 Antigens; D006649:Histocompatibility Antigens; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes