Increased extrafollicular expression of the B-cell stimulatory molecule CD70 in HIV-1-infected individuals

Objective: CD70 molecules expressed by activated T cells provide potent B cell stimulatory signals. We hypothesized that an altered CD70 expression might contribute to B cell abnormalities during HIV-1 infection. Design: CD70 expression and the functional and migratory properties of the CD4+CD70+ T lymphocytes were analyzed in HIV-1-infected patients and in humanized mice. Correlations were tested between CD70 expression and features of B-cell activation, apoptosis sensitivity and functional exhaustion. Methods: CD4+CD70+ T cells were analyzed in cohorts of CD4+ T-cell lymphopenic, viremic or nonlymphopenic, nonviremic HIV-1-infected patients and in noninfected individuals. CD70 upregulation was also followed in HIV-1-infected humanized mice. CD38, CD95, LAIR1 and PD-1 expressions were monitored on B-cell subpopulations, Ki67 was assessed to estimate B-cell proliferation and antibody levels were measured in plasma. Results: Blood CD4+CD70+ T-cell frequencies increased in response to CD4+ T-cell depletion or high viremia levels as a possible consequence of increased activation and proliferation in this subset. CD4+CD70+ T cells produced T-helper 1-type cytokines and expressed chemokine receptors mobilizing toward sites of inflammation but not to lymphoid follicles. High CD70 expression was observed in HIV-1-infected humanized mice at extrafollicular sites (peritoneum, bone-marrow). CD4+CD70+ T-cell frequencies correlated with the expression of the activation marker CD38 and the death receptor CD95 on various memory B-cell subsets, with B-cell proliferation and with plasma IgG levels. Conclusions: CD4+CD70+ T cells may contribute to B cell hyperactivation and accelerated memory B-cell turnover during HIV-1 infection. © Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved.