Signalling via the TCR/CD3 Antigen Receptor Complex in Uremia Is Limited by the Receptors Number

Abstract

The TCR/CD3 receptor complex plays a key role in antigen recognition and T-cell activation. Therefore, the present study investigates TCR α/β (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-1β 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.

Cellular Immunity in Hemodialysis Patients: A Quantitative Analysis of Immune Cell Subsets by Flow Cytometry

“…A recent paper [17] revealing altered TCR V(3 usage in HD patients considers direct effects of uremic toxins, metabolic abnormalities, the effect of dialyzer membranes or cytokines, and the increased contact with infectious agents and their toxins. Another investigation [18] considers that the number ofTCR/CD3 receptors on uremic CD4+ lymphocytes is downregulated by the ure mic milieu. The presence of blocking factors in uremic serum, which could specifically inhibit the expression of lymphocyte surface markers, including TCR/CD3 recep tors, has not yet been clarified.…”

“…Noteworthy, there is only few informa tion concerning the TCR/CD3 complex in patients with CRF [17,18].…”

Aspects of Immune Dysfunction in End-stage Renal Disease

“…Studies performed in vitro show that T-cell proliferation is decreased in the uremic milieu (45,46). As mentioned, T helper lymphocytes (Th) play a crucial role in controlling the immune response.…”

Increasing Haemodialytic Clearances as Residual Renal Function Declines: An Incremental Approach

“…HD patients are more susceptible to not only access-related but other forms of infection including respiratory tract infections, due to a combination of increased extravascular lung water, closer exposure to other patients and an altered immune system. HD patients not only have reduced responses to vaccinations, but also increased background pro-inflammatory state, characterised by increased interleukin 1, interleukin 6 and tumour necrosis factor-α [27,28] and complement on the one hand and downregulated interleukin 2 synthesis [29], ICAM-1 and TCR1/CD3 receptor expression on T-helper cells [30], and dysregulation of the Th1 and Th2 balance on the other, then impairs the response to pathogens [31]. Data from matched daily home and thrice-weekly in-centre cohorts reported a significant greater risk of first infection-related admission for the daily group [32].…”