Increased proportions of B cells with spontaneous production of interleukin-10 in HIV-infected individuals are normalized during combination antiretroviral therapy: a longitudinal study.

Interleukin-10 (IL-10)-producing B cells (B10 cells) may inhibit HIV-specific T cells and are elevated in untreated HIV infection. We aimed to determine the effect of combination antiretroviral treatment (cART) on the proportion of B10 cells. Furthermore, we compared B10-cell proportions in HIV-infected progressors and viremic controllers. This was a prospective study including HIV-infected progressors, viremic controllers and healthy controls. Progressors initiating cART were followed for 6 months. Purified B cells were stimulated with CpG, alone or in combination with HIV gp120, and the proportion of B10 cells was measured by flow cytometry. Without stimulation, the B10-cell proportion was higher in progressors than in healthy controls, while viremic controllers and healthy controls had comparable proportions. Moreover, the proportion of CD24hi CD38hi transitional B cells was higher in progressors than in healthy controls. After initiation of cART, the proportion of B10 cells and transitional B cells decreased. In conclusion, progressors had elevated B10-cell proportions, while viremic controllers displayed normal proportions. After initiation of cART, the B10-cell proportion decreased. This could limit B10-cell-mediated suppression of specific CD8+ T-cell responses.

Reduced IL-7R T Cell Expression and Increased Plasma sCD127 in Late Presenting HIV-Infected Individuals.

BACKGROUND: Late presentation of HIV infection is associated with reduced chance of optimal immune recovery after initiating combination antiretroviral therapy (cART). Interleukin-7 (IL-7) and the corresponding receptor, IL-7 receptor (IL-7R) made up of CD127 and CD132, are crucial for T cell homeostasis. This study aimed to describe IL-7R and IL-7 before and after initiation of cART in late presenting HIV-infected individuals, and the impact on immune recovery and T cell subset distribution after initiation of cART. METHODS: A total of 100 HIV-infected individuals initiating cART were included in a prospective study. Samples were collected at baseline and after 6, 12, and 24 months of cART. Proportion and expression {[median fluorescence intensity (MFI)]} of IL-7R on T cells, and plasma concentrations of soluble CD127 (sCD127) and IL-7 were determined. RESULTS: The IL-7R expression was reduced in late presenters with CD4 cell count <200 cells per microliter compared with nonlate presenters and healthy controls as demonstrated by lower proportion of CD127 + CD132 + T cells and lower CD127 MFI. In contrast, plasma sCD127 was higher. These differences were partly reversed after suppressive cART. Interestingly, the CD127 MFI on CD4 T cells was found to be a predictor of increased thymic output after 24 months of suppressive cART. CONCLUSIONS: Severely altered IL-7R expression was found in late presenters, and associations between IL-7R expression and thymic output after 24 months of suppressive cART indicate an impact of a IL-7 response for the long term de novo production from thymus.