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Kidney Int Suppl. 2001 Feb;78:S206-11.

Molecular aspects of T- and B-cell function in uremia.

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1
Medical Department IV, University of Homburg/Sarr, Saar, Germany.

Abstract

Chronic renal failure is associated with severe alterations of the immune system. Infections are responsible for a large part of the mortality in hemodialysis patients, and vaccination is mostly ineffective. Global tests of the immune function show greatly diminished activation of T cells. However, the intrinsic function of T and B cells is normal when they are provided with normal signaling from antigen-presenting cells (APCs). Patients with chronic renal failure show a defective function of costimulation derived from APCs leading to impaired activation of effector lymphocytes. Two major components of immune deviation are relevant: reduced signaling caused by impaired expression of the costimulatory molecule B7-2 (CD86) on monocytes leads to low activation of helper T cells. This dysfunction is associated with uremia and may be improved by high-efficiency renal replacement therapy. The other component is inflammatory activation of APCs mainly due to the hemodialysis procedure. Inflammation, characterized by overproduction of cytokines such as interleukin-1beta (IL-1beta) or IL-6, correlates with low effector activation. Furthermore, inflammatory cytokines such as IL-12 deviate the functional pattern of T-cell activation toward Th1 differentiation, thus leading to an additional reduction of Th2- and B-cell function. The individual severity of inflammatory alterations is partially controlled by the negatively regulating cytokine IL-10, which, on a genetic basis, can be up-regulated to a different extent in individual patients. Therapeutic interventions to improve immune dysfunction include the enhancement of dialysis efficiency and the reduction of inflammatory alterations by the use of highly biocompatible dialyzers.

[Indexed for MEDLINE]

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