Signalling via the TCR/CD3 antigen receptor complex in uremia is limited by the receptors number.
The TCR/CD3 receptor complex plays a key role in antigen recognition and T-cell activation. Therefore, the present study investigates TCR alpha/beta (TCR1) and CD3 receptor density (RD, number of receptors per cell) on uremic helper-inducer (CD4) T lymphocytes in relation to T-cell proliferative response induced by anti-CD3 monoclonal antibodies (mAb). We found, that: (1) the number of TCR/CD3 receptors on uremic helper-inducer (CD4) T lymphocytes is decreased and correlated well with the blunted lymphocyte proliferation induced by anti-CD3 mAb; (2) these findings were associated with diminished binding capacity of IL-1 beta and IL-6 to their receptors (IL-1R, IL-6R) on helper-inducer T cells, whereas (3) the IL-2 receptor (IL-2R) and molecule expression of CD4 and lymphocyte function antigen-1 (LFA-1) were increased, and (4) uremic monocytes displayed a decreased density of intercellular adhesion molecule-1 (ICAM-1) expression, which interacts as receptor-ligand pair with LFA-1. The incubation of uremic and control peripheral blood mononuclear cells with uremic serum enhanced these above-mentioned changes in the expression of examined receptors and molecules. These data might also support the hypothesis that the blunted T-cell response to antigen in uremia is due to downregulation of the TCR/CD3 receptor complex by uremic milieu.
Stachowski
J
J
Department of Nephrology, University of Cologne, FRG.
Pollok
M
M
Burrichter
H
H
Spithaler
C
C
Baldamus
C A
CA
D000328:Adult; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002455:Cell Division; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology; D017472:Receptors, Interleukin-1 / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology; D019947:Receptors, Interleukin-6; D015398:Signal Transduction / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014511:Uremia / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D015375:Receptors, Interleukin-2; D019947:Receptors, Interleukin-6