Differing regulation and function of ICAM-1 and class II antigens on renal tubular cells.
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-gamma) 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-gamma 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.
Jevnikar
A M
AM
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Wuthrich
R P
RP
Takei
F
F
Xu
H W
HW
Brennan
D C
DC
Glimcher
L H
LH
Rubin-Kelley
V E
VE
D000818:Animals; D000911:Antibodies, Monoclonal; D015551:Autoimmunity / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology*; D015342:DNA Probes; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1; D007687:Kidney Tubules, Proximal / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000032:analysis; D011991:Receptors, Virus / Q000276:immunology
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D015342:DNA Probes; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D011991:Receptors, Virus; D018799:Intercellular Adhesion Molecule-1