The selection of effector T cell phenotype by contrasuppression modulates susceptibility to autoimmune injury

C. J. Kelly, H. Mok, E. G. Neilson

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The genetic susceptibility to murine αTBM disease is a dominant trait that maps to H-2K. In previous studies we have shown that the critical difference between susceptible (SJL) and nonsusceptible (B10.S(8R)) mice is the phenotype of the tubular Ag-specific effector T cells (T(DTH)). In SJL mice, these T(DTH) are Lyt-2+, whereas in B10.S(8R) mice the T(DTH) are L3T4+. These phenotypic differences have an important functional correlate: Lyt-2+ T(DTH) are nephritogenic, whereas L3T4+ T(DTH) are typically not nephritogenic. Both mouse strains have the potential to differentiate both L3T4+ and Lyt-2+ T(DTH). The preferential selection of a single T(DTH) phenotype in each is the result of differential T cell regulation. In the present studies, we have examined the contribution of suppressor and contrasuppressor T cells in the regulation of T(DTH) phenotype selection. Our studies show that in both SJL and B10.S(8R) mice, after exposure to Ag, a suppressor T cell subpopulation functions to inhibit the nephritogenic Lyt-2+ T(DTH). In SJL, but not B10.S(8R) mice, this suppression is counterbalanced by Lyt-2+, Vicia Villosa lectin-adherent T cells. Such contrasuppressor function is mediated through a T cell-derived soluble protein (TcsF), which is Ag-binding and recognized by αI-J(s) antisera. This functional TcsF activity maps, as does susceptibility to disease, to H-2K. In the presence of genetically compatible TcsF, the T(DTH) phenotype in nonsusceptible mice switches to that of susceptible mice. These Lyt-2+ T(DTH) from nonsusceptible mice are fully capable of inducing tubulointerstitial nephritis following adoptive transfer. Our studies describe a new role for Tcs cells and augment our understanding of their etiopathogenetic role in autoimmunity.

Original languageEnglish (US)
Pages (from-to)3022-3028
Number of pages7
JournalJournal of Immunology
Volume141
Issue number9
StatePublished - 1988

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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