IL-23 signaling in Th17 cells is inhibited by HIV infection and is not restored by HAART: Implications for persistent immune activation.

Objectives: HIV infection causes a profound depletion of gut derived Th17 cells, contributing to loss of mucosal barrier function and an increase in microbial translocation, thus driving systemic immune activation. Despite normalization of circulating CD4+ T cell counts with highly active antiretroviral therapy (HAART), Th17 frequency and function often remain impaired. Given the importance of interleukin (IL)-23 in the generation and stabilization of Th17 cells we hypothesized that impaired IL-23 signaling causes persistent Th17 dysfunction in HIV infection.

Polymeric IgA-secreting and mucosal homing pre-plasma cells in normal human peripheral blood.

Clear identification of recently activated mucosal B cells in human blood would greatly facilitate study of mucosal vaccines, immune response to infection and the ongoing mucosal IgA response. We examined blood lymphocytes from normal, healthy individuals to identify IgA-secreting pre-plasma cells' (PPC) functional and phenotypic relevance to mucosal antibody production, in the absence of infection, disease or recent vaccination. PPC are the most recently activated B lymphocytes in blood and are considered in transit between lymphoid tissue and effector tissues, where they terminally differentiate into plasma cells.

Stimulation of anti-polio and anti-HSV IgA pre-plasma cell response in blood following parenteral immunization with tetanus-diphtheria vaccine.

Systemic immunization can elicit a significant response of IgG producing activated B cell subsets in human blood, part of which is not toward the vaccine. However, the effect of vaccination on IgA antibody secreting B cell subsets has had limited investigation. We immunized healthy, adult volunteers with a tetanus/diphtheria vaccine and observed a significant burst of IgA-secreting pre-plasma cells (PPC).