Background. The immunosuppressive state of hemodialysis (HD) patients is accompanied by activation of antigen-presenting cell-derived cytokines, for example, tumor necrosis factor-α (TNF-α), which are required for T-cell activation. To test whether an activated TNF-α system results in impaired T-cell response in these patients, we analyzed parameters of their antigen-presenting cell (APC) function (for example, TNF-α system) and T-cell function [for example, interleukin-2 (IL-2) system]. Methods. By quantitative flow cytometry, the expression of the TNF-receptor 2 (TNF-R2 = CD120b) and the α and β chain of the IL-2 receptor (IL-2R: CD25, CD122) was measured. Using reverse transcriptase-polymerase chain reaction, the mRNA for TNF-α, IL-2, and IL-2R were determined. Phytohemagglutinin (PHA)- and IL-2-stimulated proliferation and cytokine production were measured. Biological activity of soluble receptors was measured by adding recombinant cytokines to the patient's plasma. Results. CD120b expression was significantly increased in HD patients, whereas CD25 and CD122 was comparable to controls. In contrast to mRNA for 1L-2 and IL-2R, mRNA for TNF-α was increased in HD. This resulted in significantly increased TNF-α levels in HD patients. In peripheral blood of HD patients, high levels of soluble TNF-R (R1 and R2) and IL-2R were found. These receptors were capable of binding 40% of added TNF-α and 55% of added IL-2. PHA-induced TNF-α production by T cells from HD patients was significantly lower, while their PHA-stimulated IL-2 production and proliferation capacity by T cells were comparable to controls. Conclusions. We conclude that although the TNF-α system is activated during HD, the TNF-α production of T cells is impaired, suggesting that tachyphylaxis of T cells occurs for TNF-α, as their proliferative capacity and IL-2 production capacity do not imply an intrinsic T-cell defect.

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Kidney International
Department of Virology

van Riemsdijk, I.C, Baan, C.C, Loonen, E.H.M, Knoop, C, Betonico, G.N, Niesters, H.G.M, … Weimar, W. (2001). T cells activate the tumor necrosis factor-α system during hemodialysis, resulting in tachyphylaxis. Kidney International, 59(3), 883–892. doi:10.1046/j.1523-1755.2001.059003883.x