Differing regulation and function of ICAM-1 and class II antigens on renal tubular cells

Anthony M. Jevnikar, Rudolf P. Wuthrich, Fumio Takei, Hong Wu Xu, Daniel C. Brennan, Laurie H. Glimcher, Vicki E. Rubin-Kelley

Research output: Contribution to journalArticlepeer-review

Abstract

Intercellular adhesion molecule-1 (ICAM-1) and MHC class II (Ia) antigens are increased on proximal tubular epithelial cells (TEC) in autoimmune nephritis and transplant rejection. ICAM-1 is a member of the immunoglobulin gene superfamily that increases the avidity of T cell interactions with antigen-presenting cells bearing Ia antigens. Using an existing mAb and cDNA probe for Ia antigen, and a newly described mAb (YN1/1.7.4) and cDNA probe for murine ICAM-1, we compared mRNA transcript levels, surface expression and function of these molecules in transformed TEC derived from normal (C3H/FeJ) and autoimmune (MRL-lpr) mice. No differences were found on TEC between these strains of mice. Stimulation of TEC with interferon-gamma (IFN-γ) resulted in the expression of Ia antigens, and a marked increase of ICAM-1 from basal levels. Increases in ICAM-1 levels occurred with concentrations of IFN-γ 10 to 100 times lower (0.5 to 1.0 U/ml) than those required for Ia expression, and preceded Ia antigen expression by more than 48 hours. Anti-ICAM-1 mAb lowered the binding and antigen-presenting ability of TEC to the A2A2 T cell hybridoma, suggesting a role for ICAM-1 in immune interactions between TEC and T cells. Dexamethasone treatment of MRL-lpr mice abrogated the increase of Ia antigens found in the kidneys of nephritic mice yet did not reduce the expression of ICAM-1 in either kidneys or cultured stimulated TEC. We conclude that elevated ICAM-1 expression on TEC increases the immune accessory cell capability of TEC bearing Ia antigens, and is resistant to down-regulation by some immunosuppressive agents.

Original languageEnglish (US)
Pages (from-to)417-425
Number of pages9
JournalKidney international
Volume38
Issue number3
DOIs
StatePublished - Sep 1990
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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