T cells activate the tumor necrosis factor-alpha system during hemodialysis, resulting in tachyphylaxis

Background. The immunosuppressive state of hemodialysis (HD) patients is ac companied by activation of antigen-presenting cell-derived cytokines, for e xample, tumor necrosis factor-alpha (TNF-alpha), which are required for T-c ell activation. To test whether an activated TNF-alpha: system results in i mpaired T-cell response in these patients, we analyzed parameters of their antigen-presenting cell (APC) function (for example, TNF-alpha 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 alpha and beta chain of the IL-2 receptor (IL- 2R; CD25, CD122) was measured. Using reverse transcriptase-polymerase chain reaction, the mRNA for TNF-alpha, IL-2, and IL-2R were determined. Phytohe magglutinin (PHA)- and IL-2-stimulated proliferation and cytokine productio n were measured. Biological activity of soluble receptors was measured by a dding recombinant cytokines to the patient's plasma. Results. CD120b expression was significantly increased in HD patients, wher eas CD25 and CD122 was comparable to controls. In contrast to mRNA for IL-2 and IL-2R, mRNA for TNF-alpha was increased in HD. This resulted in signif icantly increased TNF-a levels in HD patients. In peripheral blood of HD pa tients, high levels of soluble TNF-R (R1 and R2) and IL-2R were found. Thes e receptors were capable of binding 40% of added TNF-alpha and 55% of added IL-2. PHA-induced TNF-alpha production by T cells from HD patients was sig nificantly lower, while their PHA-stimulated IL-2 production and proliferat ion capacity by T cells were comparable to controls. Conclusions. We conclude that although the TNF-alpha system is activated du ring HD, the TNF-a production of T cells is impaired, suggesting that tachy phylaxis of T cells occurs for TNF-alpha, as their proliferative capacity a nd IL-2 production capacity do not imply an intrinsic T-cell defect.