No evidence for abnormal immune activation in peripheral blood T cells in patients with hepatitis C virus (HCV) infection with or without cryoglobulinaemia

Abstract

SUMMARYThe aim of this study was to investigate the peripheral blood lymphocyte (PBL) phenotypes and T cell repertoire in patients with HCV infection, with or without mixed cryoglobulinaemia (MC). The patients were: Group 1, 23 patients with HCV infection and MC; Group 2, 14 patients with HCV infection but without MC; Group 3, 10 patients with symptomatic essential MC. Twenty healthy blood donors were used as controls. Blood lymphocyte counts were determined, and flow cytometry was used to measure proportions of B cellsBias in the usage of T cell receptor (TCR) Vb chains was studied in a subgroup of 10 representative patients of Group 1 using a polymerase chain reaction (PCR) analysis of the Vb segments with a series of 20 oligonucleotides specific for the Vb families. The three groups were comparable for blood lymphocyte counts, and we observed no abnormal repartition of the following PBL subsets: T cells (CD3 þ ), CD4 þ and CD8 þ subpopulations, B cells (CD19 þ ), and the NK cells (CD16 þ 56 þ ). In none of the groups could we observe lymphocyte ex vivo activation as assessed by the normal expression of the activation cell markers: CD25 on CD4 þ or CD8 þ T cells, or CD5 on B cells. The repartition of naive and memory (CD45RO ¹ /RO þ ) CD4 þ T cells was normal and we did not observe any amplification of the CD4 þ CD7 ¹ T cell subset differentiated in vivo in Th0/Th2 cells. There was no significant amplification of cytotoxic (SF6 þ ) and immunoregulatory (CD57 þ ) CD8 þ T cells in HCV patients with or without MC. Finally, the usage of Vb families in the TCR repertoire was normal in the patients tested. In patients with chronic HCV infection, with or without MC, we did not find any significant expansion or abnormal activation of T, B and NK cell subsets, dysbalance of the naive/ memory subsets, or expansion of the Th0/Th2 subpopulation. These findings differ from the profound immune alterations that are observed in other chronic infections such as HIV or Epstein-Barr virus. Although this study was restricted to the peripheral blood, it suggests that in chronic HCV infection, MC is not the consequence of a chronic activation or dysregulation of the peripheral blood immune cells.

T‐lymphocyte populations in hepatitis C and HIV co‐infected patients treated with interferon‐alfa‐2a and ribavirin

“…These data suggest that defective DC function may result in the poor CD4 proliferative responses [28], the impaired CD8 cytotoxic responses to HCV antigens and the low level of lymphocyte activation in blood [29–31]. In addition, differences between blood and liver DC may account for the presence of HCV specific and activated T‐cells in much higher proportion in liver than in blood [32,33]. We cannot explain why the CD4 DR percentage was significantly higher in HCV mono‐infected patients than co‐infected subjects.…”

Altered T-cell subsets in HIV-1 natural viral suppressors (elite controllers) with hepatitis C infection

“…HCV has not been reported to cause a decreased CD4 count or increased immune activation in HCV mono-infected individuals [10]. However, we hypothesize that in the setting of HIV infection, HCV co-infection can increase immune activation, and cause T cell disturbances (decreased CD4 count, decreased naïve T cells, increased effector T cells).…”

Association of Chronic Hepatitis C Infection With T-Cell Phenotypes in HIV-Negative and HIV-Positive Women

“…Most of these studies found no differences in the percentage of CD4+ and CD8+ T-cells that were activated by HCV status, 14-17 although one study found that CD4+ T-cell activation was higher in those with HCV viremia. 18 Comparisons of the percentage of regulatory CD4+ T-cells (Tregs) between individuals with HCV viremia and HCV-uninfected controls have also been conducted but the data have conflicted.…”