Abstract
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.
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