Supplementary MaterialsSupplementary Files 41598_2019_43311_MOESM1_ESM

Supplementary MaterialsSupplementary Files 41598_2019_43311_MOESM1_ESM. bloodstream and RM had been single IL-17A makers or dual-cytokine makers (IL-17A+TNF-+). In another cohort of 21 HIV positive males, we noticed identical cells distributions of Tc and Th cell subsets, although Tc17 cell frequencies both in cells and blood were suprisingly low. Higher frequencies of multi-cytokine-producing Th17 and Tc17 cells in RM of HIV adverse men positively correlated with increased mucosal HIV target cells, suggesting a need to further characterize the effector functions of these cells and their role in HIV acquisition and pathogenesis. studies demonstrating an increased susceptibility to HIV infection12,17. CD8 T cells are similarly diverse in their capacity to differentiate into distinct functional phenotypes. The cytokines produced by the Tc subsets, i.e. Tc1, Tc2, and Tc17 cells, mirror those secreted by their CD4 counterparts. HIV transmission triggers the activation and differentiation of CD8 T cells, which Sodium stibogluconate results in a robust cytotoxic response, primarily from Tc1 cells, that fails to prevent infection but does serve to slow disease progression18. Tc17 cells, a more recently discovered and less well characterized CD8 T cell subset, share important features with Th17 cells. Both subsets predominate in the intestinal mucosa, secrete IL-17A, and appear to play a role in Rabbit polyclonal to SUMO3 protecting intestinal mucosal integrity. In prior studies, Tc17 cells have demonstrated the capacity to produce multiple cytokines, including IL-2 and TNF-, while exhibiting few cytotoxic effects, compared to Tc1 and Tc2 cells, as they lack expression of perforin and granzyme B19C21. At this time, there is a paucity of information Sodium stibogluconate about the effector functions of these cells and their role in host defense against viral pathogens, including HIV. In this study, we sought to determine the frequency, phenotype, and functional profiles of CD4 and CD8 T cell subsets in the peripheral blood and rectal mucosal tissue compartments of healthy HIV negative men, focusing primarily on the IL-17A-producers, Th17 and Tc17 cells. In addition, we examined the tissue distribution of these cell subsets in a separate cohort of HIV positive men with preserved peripheral blood CD4 counts. We hypothesized that the composition and functional activity of CD4 and Sodium stibogluconate CD8 T cell subsets would be distinct within the blood and rectal mucosal tissue compartments. Results Th2, Th17 and Tc17 cell subsets are predominant in the rectal mucosa compared to peripheral blood of HIV negative men We investigated the frequencies of IFN–, IL-4-, and IL-17A-producing CD4 and CD8 T cells in blood and rectal mucosa from 62 healthy, HIV negative men to determine if there are compartmental differences in the distribution of these cell subsets. Isolated mononuclear cells from peripheral blood and rectal mucosal samples were stimulated with phorbol myristate acetate (PMA) and Ionomycin to induce cytokine production by the total T cell population. Using an intracellular cytokine assay and multi-color flow cytometry, the levels of IFN–producers (Th1 or Tc1 for IFN–secreting CD4 or CD8 T cells, respectively), IL-4-producers (Th2 or Tc2 for IL-4-secreting CD4 or CD8 T cells, respectively), and IL-17A-producers (Th17 or Tc17 for IL-17A-secreting CD4 or CD8 T cells, respectively) were quantified (Fig.?S1). The median frequencies of Th17 (1.21 vs 0.26; p? ?0.0001), Th2 (3.6 vs 0.26; p? ?0.0001), and Tc17 (0.48 vs. 0.01; p? ?0.0001) subsets were significantly higher within the rectal mucosa set alongside the bloodstream area (Fig.?1). There have been overall hardly any IL-4- (Tc2) and IL-17A- (Tc17) creating Compact disc8 T cells seen in the peripheral bloodstream. The frequencies of Tc1 and Th1 cells were similar between your.