Immune defects in chronic renal impairment: evidence for defective regulation of lymphocyte response by macrophages from patients with chronic renal impairment on haemodialysis.
Cellular mechanisms contributing to impaired lymphocyte proliferative responses in chronic renal impairment (CRI) were investigated using peripheral blood mononuclear cells (PBMC) from 25 patients receiving haemodialysis. Impaired T cell proliferative responses to phytohaemagglutinin were demonstrated. The hyporeactive PBMC from patients with CRI suppressed the responses of PBMC from normals to a greater degree than did control PBMC. This immunosuppression was reversed significantly by depleting adherent monocytes (M phi). To further determine if these impairments might be critically dependent on cell-cell contact, M phi from an additional 10 patients on haemodialysis were examined for ability to support B and T cell colony formation in semi-solid cultures stimulated by Staphylococcus protein A (SpA). When compared to normal controls, significantly fewer B and T cell colonies were observed with M phi from CRI patients than when autologous M phi were used. Also, T cells from patients were significantly less effective than controls in supporting B cell colony growth. Decreased T and B cell colony responses in patients were not due to a primary abnormality of these cells, since allogeneic mixing experiments showed that B and T cells from patients were able to form a sufficient number of colonies when control M phi or T cells from normals were used as accessory and helper cells. These findings suggest that although M phi-mediated suppressor activity is an important mechanism contributing to impaired lymphocyte responsiveness in patients with chronic renal impairment on haemodialysis, additional or related abnormalities in M phi 'accessory' function may also exist.
D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000628:therapy; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D006435:Renal Dialysis; D013205:Staphylococcal Protein A / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D013205:Staphylococcal Protein A