CD4+CXCR5+ T cells in chronic HCV infection produce less IL-21, yet are efficient at supporting B cell responses

Background & Aims: During chronic HCV infection, T cell dependent virus-specific antibodies are produced. However, the role of B-T cell interaction in chronic HCV is largely unknown. CD4+CXCR5+ T follicular helper (TFH)-cells activate B cells and are important for clearance of various chronic viral infections. We investigated the function of TFH cells and B cells in liver and in peripheral blood of chronic HCV patients. Methods: T cells from chronic HCV patients and healthy individuals were analysed for expression of CXCR5, PD-1, ICOS, and IL-21 and IFN-c production by flow cytometry. CD19+ B cell subpopulations were identified on the basis of CD27 and IgD expression. In order to assess the frequency and function of T cells and B cells in liver follicles, immunohistochemistry was performed for CD3, CXCR5, Bcl6, IL-21, CD20, IgD, IgM, and IgG. Results: The frequency of IL-21-producing CXCR5+CD4+ T cells in blood was lower in HCV patients compared to healthy individuals (p = 0.002), which was reflected by lower serum IL-21 levels (p <0.001). Nonetheless, CXCR5+CD4+ T cells from HCV patients and healthy individuals were equally capable to stimulate CD19+CD27+ memory B cells into IgG and IgM-producing plasmablasts. Importantly, human intrahepatic TFH cells and their related function were identified by immunohistochemistry on liver biopsies for CD3, Bcl6, and CD20 within portal areas and follicles. Conclusions: The specific localization of TFH cells and IgG and IgD/IgM-producing B cells suggests a functional B-T cell environment in liver follicles during HCV infection. The decreased frequency of IL-21-producing CXCR5+CD4+ T cells and lower serum IL-21 levels in chronic HCV patients did not lead to an altered TFH-B cell interaction.

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