Spontaneous interstitial nephritis in kdkd mice. II. Characterization of a tubular antigen-specific, H-2K-restricted Lyt-2+ effector T cell that mediates destructive tubulointerstitial injury.
In this report, we have examined the effector T cell repertoire in the spontaneous interstitial nephritis of kdkd mice. Lymph node cells from nephritic kdkd mice are capable of transferring this disease into thymectomized, irradiated, and bone marrow-reconstituted CBA/Ca recipients. CBA/Ca mice do not spontaneously develop interstitial nephritis and are normally resistant to the adoptive transfer of nephritic cells, a resistance that in the short term can be attenuated with low-dose cyclophosphamide. We therefore used delayed-type hypersensitivity responses and direct transfer of immune cells under the renal capsule to characterize nephritogenic effector cells from kdkd donor mice. Lyt-2+, L3T4- T cells from the peripheral lymphoid organs of nephritic kdkd mice, after adoptive transfer into cyclophosphamide-pretreated CBA/Ca recipients, mediate an antigen-specific delayed-type hypersensitivity response to renal tubular basement membrane antigens. These cells are restricted by gene products in H-2Kk; they are also present in nephritic, but not in control kidneys. We have also observed this same phenotypic subpopulation of kdkd lymphocytes mediate a destructive interstitial renal lesion within 7 days of being placed under the kidney capsule of CBA/Ca mice. These findings suggest that T lymphocytes reactive to a parenchymal tubular antigen are of substantial importance in the development of spontaneous interstitial nephritis in kdkd mice.
C J
CJ
Kelly
R
R
Korngold
R
R
Mann
M
M
Clayman
T
T
Haverty
E G
EG
Neilson
D000818:Animals; D000941:Antigens / Q000276:immunology*; D000950:Antigens, Ly; D001485:Basement Membrane / Q000276:immunology / Q000473:pathology; D000939:Epitopes / Q000276:immunology; D006183:H-2 Antigens / Q000235:genetics* / Q000276:immunology; D006968:Hypersensitivity, Delayed; D007116:Immunization, Passive; D007684:Kidney Tubules / Q000276:immunology / Q000473:pathology; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains; D009395:Nephritis, Interstitial / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D010641:Phenotype; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*
D000941:Antigens; D000950:Antigens, Ly; D000939:Epitopes; D006183:H-2 Antigens; C024755:H-2K(K) antigen; C035812:renal tubular antigen