T cell receptor Vβ genes expressed by IgG anti‐DNA autoantibody‐inducing T cells in lupus nephritis: Forbidden receptors and double‐negative T cells

Sharlene Adams, Tracy Zordan, Krishna Sainis, Syamal K. Datta*

*Corresponding author for this work

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

In the (SWR × NZB)F1 (SNF1) model of lupus nephritis, pathogenic variety of IgG anti‐DNA autoantibodies are induced by certain T helper (Th) cells that are either CD4+ or CD4CD8 (double negative; DN) in phenotype. From the spleens of eight SNF1 mice with lupus nephritis, 149 T cell lines were derived and out of these only 25 lines (≈ 17%) were capable of augmenting the production of pathogenic anti‐DNA autoantibodies. Herein, we analyzed the T cell receptor (TcR) Vβ genes used by 16 such pathogenic autoantibody‐inducing Th cell lines. Twelve of the Th lines were CD4+ and among these five lines expressed Vβ8 (8.2 or 8.3). The Vβ8 gene family is contributed by the NZB parent to the SNF1 mice, since it is absent in the SWR parental strain. Three other CD4+ Th lines expressed Vβ4, another was Vβ2+ and one line with poor autoantibody‐inducing capability expressed Vβ1. Four autoantibody‐inducing Th lines from the SNF1 mice had a DN phenotype and these lines were also autoreactive, proliferating in response to syngeneic spleen cells. Among these DN Th lines, two expressed Vβ6 and one expressed Vβ8.1 TcR. Both of these are forbidden TcR directed against Mls‐1a (Mlsa) autoantigens expressed by the SNF1 mice and such autoreactive T cells should have been deleted during thymic ontogeny. Thus, the DN Th cells of non‐lpr SNF1 mice are different from the DN cells or MRL‐lpr which lack helper activity and do not express forbidden TcR. The spleens of 6 out of 19 nephritic SNF1 animals tested also showed an expansion of forbidden autoreactive TcR+ cells that were mainly DN. Two of these animals expressed high levels of Vβ6 (anti‐Mlsa) and Vβ11 (anti‐I‐E) TcR+ cells, three others had high levels of Vβ11+ cells alone and one animal had an expanded population of Vβ17a+ (anti‐I‐E) cells. The I‐E‐reactive TcR again should have been eliminated in the SNF1 thymus, since they express I‐E molecules contributed by the NZB parent. The SWR parents of SNF1, are I‐E; moreover, they lack the Vβ11 gene but they express Vβ17a in peripheral T cells. Whereas the NZB parents are I‐E+, they lack a functional Vβ17a gene and they delete mature Vβ11+ T cells. Thus, a combination of MHC class II and TcR genes inherited from the NZB and SWR parents and abnormalities in thymic deletion/selection processes may generate the autoantibody‐inducing Th cells in the SNF1 mice.

Original languageEnglish (US)
Pages (from-to)1435-1443
Number of pages9
JournalEuropean Journal of Immunology
Volume20
Issue number7
DOIs
StatePublished - Jul 1990

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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