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

J Immunol. 1986 Jan;136(2):526-31.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens / immunology*
  • Antigens, Ly*
  • Basement Membrane / immunology
  • Basement Membrane / pathology
  • Epitopes / immunology
  • H-2 Antigens / genetics*
  • H-2 Antigens / immunology
  • Hypersensitivity, Delayed
  • Immunization, Passive
  • Kidney Tubules / immunology
  • Kidney Tubules / pathology
  • Mice
  • Mice, Inbred A
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Mutant Strains
  • Nephritis, Interstitial / genetics
  • Nephritis, Interstitial / immunology*
  • Nephritis, Interstitial / pathology
  • Phenotype
  • T-Lymphocytes / classification
  • T-Lymphocytes / immunology*

Substances

  • Antigens
  • Antigens, Ly
  • Epitopes
  • H-2 Antigens
  • H-2K(K) antigen
  • renal tubular antigen