Lymphocyte adhesion molecules in T cell-mediated lysis of human kidney cells

M. G. Suranyi, G. A. Bishop, C. Clayberger, A. M. Krensky, P. Leenaerts, G. Aversa, B. M. Hall

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

The complementary adhesion molecules LFA-I (CD11a, 18)/ICAM-1 (CD54) and LFA-2 (CD2)/LFA-3 (CD58) have been shown to be important in T cell interaction with lymphoid target cells. The role of these ligand pairs in cytotoxicity against somatic cells is less well established. While LFA-3 is expressed by all cells in the kidney, ICAM-1 expression is low in normal kidneys but is increased in allograft rejection. An in vitro cytotoxicity assay was used to examine the relative importance of the two adhesion ligands in immune damage against kidney cells in rejection. HLA-A2 specific cytotoxic T lymphocyte (CTL) recognition of cultured human kidney cells (HKC), of predominantly renal tubular cell origin, was studied. Immunofluorescence studies showed that both induced and uninduced HKC target cells expressed ICAM-I, MHC class I and LFA-3, but only MHC class I and class II antigens and ICAM-1 were significantly upregulated by cytokine induction. Effector cells expressed LFA-I and LFA-2 but little or no ICAM-1 and LFA-3. Cytokine induction of ICAM-1 expression on HKC target cells increased their susceptibility to lysis. Monoclonal antibody against ICAM-I or LFA-1 produced the greatest inhibition of HKC lysis, and their effects were not additive. Antibody against LFA-2 (CD2) or LFA-3 also produced significant inhibition, but to a lesser degree, and no additive effect was found. The combination of antibody against both adhesion bridges almost completely abrogated lysis of HKC target cells, and this was as effective as a combination of antibodies that blocked binding by the T cell receptor to target cell class I MHC. These results suggest that ICAM-1, not expressed on normal kidney cells in vivo, but significantly induced in allograft rejection, may play a significant role in increasing the susceptibility of kidney cells to immune lysis, and modulation of these interactions may protect the graft from rejection.

Original languageEnglish (US)
Pages (from-to)312-319
Number of pages8
JournalKidney international
Volume39
Issue number2
DOIs
StatePublished - Feb 1991

ASJC Scopus subject areas

  • Nephrology

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