Impaired in vitro growth of PHA induced T lymphocyte colonies in hemodialyzed renal failure patients

Chronic dialysis patients have several indices of immune deficiency. We examined the hypothesis that the biocompatibility of dialysis membranes may influence the ability of lymphocytes to express interleukin-2 (IL-2) receptors on their surface, a key event in cellular immune response. We investigated the potential role of the dialysis membrane in eight chronic hemodialysis patients. The study design was a cross-over study using cuprophane and polymethylmethacrylate (PMMA) membranes. Chronic dialysis with new cuprophane membrane leads to an increase in baseline expression of the two subunits of IL-2 receptors. IL2R alpha (p55, CD25) and IL-2R beta (p70), in peripheral blood mononuclear cell (PBMC). However, Phytohemagglutinin (PHA) stimulation of PBMC harvested after two weeks of dialysis with cuprophane membrane showed a markedly decreased expression of high affinity IL-2 receptors. These findings are reversed when patients were dialyzed with a PMMA membrane which is also associated with minimal complement activation. The increased expression of IL-2 receptor subunits are reproduced in vitro by direct contact of PBMC with cuprophane membrane and by the addition of the anaphylatoxin C5a. This study confirms the participation of lymphocytes in the complex blood-membrane interactions that occurs during dialysis; the results may be relevant to observations of immune deficiency in dialysis patients.

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T cell activation defect in hemodialysis patients: Evidence for a role of the B7/CD28 pathway

Girndt¹,

Köhler²,

Schiedhelm-Weick³

et al. 1993

Kidney International

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The immunosuppressive effect of chronic renal failure is correlated with an impaired proliferation of peripheral blood leukocytes in vitro. This is mainly due to an impaired function of the accessory cells rather than the T cells. Here we tried to define a missing accessory signal for T cell activation in hemodialysis patients. We substituted cell surface bound molecules by adding tumor cell lines to the in vitro assays that express different patterns of accessory molecules. Cell lines that express the costimulatory B7 molecule reconstituted the activation of patients' cells whereas B7 negative cells did not. The reconstitution was also achieved using mouse fibroblasts transfected with human B7 or by monoclonal antibodies that stimulate the B7 ligand CD28 on T cells. These data further emphasize that impaired leukocyte function in renal failure is due to an accessory cell defect, and that T cells of these patients have normal functional capacities when they get the costimulatory signals required. We demonstrate that it is the B7/CD28 pathway that reconstitutes cellular functions in the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

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Impaired in vitro growth of PHA induced T lymphocyte colonies in hemodialyzed renal failure patients

Cited by 3 publications

References 12 publications

The Uremic Syndrome

The Uremic Syndrome

Hemodialysis with cuprophane membrane modulates interleukin-2 receptor expression

T cell activation defect in hemodialysis patients: Evidence for a role of the B7/CD28 pathway

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