Lack of effect of chronic hepatitis C virus infection on T-cell cytokine production in chronic hemodialysis patients

Abstract

It has been shown that chronic hemodialysis modifies, to some extent, the normal immune response by both T and B lymphocytes elicited by antigenic stimulation, e.g. by impairing the T-cell-dependent response after vaccination. A new technique, i.e. flow cytometry, enables to assess intracytoplasmically, at the single cell level, the production of a given cytokine. By using it, we studied in healthy volunteers (HV) and in chronic hemodialysis (CHD) patients, with respect to their hepatitis C virus (HCV) status, the production by the T lymphocytes of type 1, and type 2 cytokines. We studied the following cytokines (CK): IL-2, IL-4, IL-5, IL-6, IL-10, IFN-gamma and TNF-alpha in the T-cell lymphocytes (whole, CD4+ and CD8+). There were 13 HV and 59 CHD patients (36 HCV(-) and 23 HCV(+)). Amongst the latter, there were 32 men and 27 women, aged 59.5 +/- 2 years, undergoing CHD since 70 +/- 9.4 months. We found that: (1) the total number of lymphocytes as well as those expressing CD3, CD4, or CD19 were significantly decreased in CHD patients as compared to those from HV; (2) the total number of lymphocytes as well as their different subsets were similar in HCV(+) and in HCV(-) CHD patients; (3) the frequency of T-cell-expressing IL-5 or IL-10 was always low (<1%) in both HV and CHD groups; (4) overall in CHD patients, the mean percentages of T lymphocytes expressing IL-2, IL-4, IFN-gamma or TNF-alpha were respectively 31 +/- 13, 2.5 +/- 1.3, 28 +/- 12 and 34 +/- 11% and were not statistically different between HCV(+) and HCV(-) patients; (5) IL-2 was mainly produced by CD4+ T cells, whereas IFN-gamma was produced by CD8+ T cells, in both HV and CHD groups, and (6) the lymphocytes of CHD patients produced significantly more IL-2 and IL-4 than those from HV, suggesting an activation of their T lymphocytes. We conclude that using the cytokine flow cytometry assay, our study demonstrated that in HCV(+) CHD patients, as opposed to what has been described for HCV(+) patients with normal renal function, there was no impairment in the production of type 1 cytokines by peripheral blood mononuclear cells when compared to HCV(-) CHD patients. Conversely to HV, T lymphocytes from CHD patients are activated.