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

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.

• Authors: M Girndt, M Sester, U Sester, H Kaul, H Köhler
• Journal: Kidney international. Supplement (Kidney Int Suppl) Vol. 78 Pg. S206-11 (Feb 2001) ISSN: 0098-6577 [Print] United States
• PMID: 11169012 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antigens, CD
• B7-2 Antigen
• CD86 protein, human
• Cytokines
• Inflammation Mediators
• Membrane Glycoproteins

Topics

• Antigen-Presenting Cells (immunology)
• Antigens, CD (metabolism)
• B-Lymphocytes (immunology)
• B7-2 Antigen
• Cytokines (biosynthesis)
• Humans
• Inflammation Mediators (metabolism)
• Kidney Failure, Chronic (immunology, therapy)
• Lymphocyte Activation
• Membrane Glycoproteins (metabolism)
• Renal Dialysis (adverse effects)
• Signal Transduction
• T-Lymphocytes (immunology)
• Uremia (immunology, therapy)