Autoreactive kidney-infiltrating T-cell clones in murine lupus nephritis

Cristina Díaz Gallo, Anthony M. Jevnikar, Daniel C. Brennan, Sandrine Florquin, Alvaro Pacheco-Silva, Vicki Rubin Kelley

Research output: Contribution to journalArticle

Abstract

T-cells have been implicated in autoimmune renal injury. To examine the role of T-cells in lupus nephritis we propagated T-cell clones from the cortical interstitium of MRL/lpr mice. All isolated kidney-infiltrating (KI) T-cell clones [6] express surface markers identical to the T-cells regulated by the lpr gene (Thy 1.2+, TCR α/β+, Lyt-2-, L3T4-, B220+). Although KI T-cell clones have the same surface markers as lymph node-infiltrating (LNI) T-cells, they differ functionally. KI T-cells, but not LNI T-cells, are autoreactive and kidney-specific. exclusively proliferating to renal tubular epithelial (TEC) and mesangial cells. In addition, unlike LNI T-cell supernatants (SN), KI T-cell clones SN induce class II and ICAM-1 on cultured TEC. When KI T-cell clones are injected under the renal capsule, class II is increased on TEC. All clones transcribe mRNA for cytokines capable of inducing class II and ICAM-1 (IL-4, TNF-α, IFN-γ). Anti-IFN-γ mAb prevents the induction of class II and ICAM-1 on cultured TEC. Since class II and ICAM-1 expression on TEC precedes renal injury, the ability to propagate autoreactive, kidney-specific T-cell clones that induce these molecules provides evidence for their role in initiating renal injury in MRL/lpr mice.

Original languageEnglish (US)
Pages (from-to)851-859
Number of pages9
JournalKidney international
Volume42
Issue number4
DOIs
StatePublished - Oct 1992
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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    Gallo, C. D., Jevnikar, A. M., Brennan, D. C., Florquin, S., Pacheco-Silva, A., & Kelley, V. R. (1992). Autoreactive kidney-infiltrating T-cell clones in murine lupus nephritis. Kidney international, 42(4), 851-859. https://doi.org/10.1038/ki.1992.360