Immunodeficiency in ESRD-patients is linked to altered IL-2 receptor density on T cell subsets.

The interdependence of blunted T cell proliferation induced by anti-CD3 monoclonal antibodies (mAb) and the preactivation of T lymphocytes (CD25+) in ESRD patients was investigated in this study. We focused on the density of IL-2 (CD25) receptors [IL-2R] on the lymphocyte surface rather than enumeration of IL-2R positive cells. The effect of exogenous IL-2 on these parameters was also tested. Blunted T lymphocyte proliferation induced by anti-CD3 mAb is only partially corrected by addition of exogenous IL-2 after 24 hrs. Freshly isolated uremic CD4 T cells show higher percentage of IL-2 positive cells and a higher IL-2R density on the cell surface compared to controls. However, after anti-CD3 mAb stimulation the number of IL-2R positive cells and IL-2R density in CD4 T subset was significantly lower than in samples from normal donors. Exogenous IL-2 had no influence on IL-2R expression on CD4 cells in uremic patients. On the other hand, following anti-CD3 mAb stimulation uremic CD8 cells reveal more IL-2R positive cells with higher IL-2R density than in controls. Moreover, exogenous IL-2 enhance IL-2R expression and density on uremic CD8 cells more than in controls. Our results suggest that the blunted T cell proliferation in ESRD patients might result from (a) preactivation of CD4 T cells, (b) diminished response of uremic CD4 T cells to IL-2, and (c) higher suppressor cells activity.