TY - JOUR
T1 - Autoreactive kidney-infiltrating T-cell clones in murine lupus nephritis
AU - Gallo, Cristina Díaz
AU - Jevnikar, Anthony M.
AU - Brennan, Daniel C.
AU - Florquin, Sandrine
AU - Pacheco-Silva, Alvaro
AU - Kelley, Vicki Rubin
N1 - Funding Information:
(VRK), CA-48626 (VRK), AI-07918 (DCB) and the Jules and Gwen Knapp Charitable foundation. Cristina DIaz Gallo is the recipient of a SANDOZ/Sociedad Espanola de NefrologIa and Fulbright-La Caixa grants; Anthony M. Jevnikar is the recipient of a fellowship from the Medical Research council of Canada; Sandrine Florquin is the recipient of a grant from the Fond National de La Recherche Scientifique, Belgium; Alvaro Pacheco-Silva is the recipient of a grant from the Conselho Nacional de Desenvolvimento CientIfico e Tecnologico (CNPq), Brazil. We wish to acknowledge Dr. C.B. Carpenter and Dr. G.G. Singer from Harvard Medical School for helpful comments and review of this manuscript. This study was presented in part and in abstract form at the American Society of Nephrology Meeting, Novem- ber, 1991.
PY - 1992/10
Y1 - 1992/10
N2 - 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.
AB - 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.
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U2 - 10.1038/ki.1992.360
DO - 10.1038/ki.1992.360
M3 - Article
C2 - 1360551
AN - SCOPUS:0026712960
SN - 0085-2538
VL - 42
SP - 851
EP - 859
JO - Kidney international
JF - Kidney international
IS - 4
ER -