BCG-primed T cells to Ag85A and those induced by environmental mycobacteria are predominantly CD4+. We did not measure MVA-specific T-cell responses in our study. We observed higher frequencies of total cytokine+, TNF-α+ and polyfunctional CD4+ T cells in adolescents, compared with children. We showed that CD4+ T-cell count, which is highest in neonates and decreases with age 26, 27, did not account for the observed differences. Rather, when we adjusted for age-specific memory CD4+ T-cell proportions, similar

frequencies were obtained between adolescents and children. This data analysis was subject to the caveat that lymphocyte or CD4+ T-cell counts or memory frequencies from individual adolescents and children studied here were not available. Instead, we classified subjects into different age categories, and adjusted FDA-approved Drug Library in vivo for the corresponding median lymphocyte or CD4 counts reported for Ugandan participants 26, or memory T-cell frequencies reported for American children 27. No published lymphocyte or memory CD4+ T-cell counts were available for South African children. Such data would have been more appropriate since co-variates such as helminth infections,

malaria, genetic and/or socioeconomic status are likely be different between South African and Ugandan or American children. Regardless, our results suggest that differential cell counts and/or relative frequencies of memory T cells should be taken into account when comparing immune responses very from children at different ages. The results also suggest that absolute numbers of Ag-specific T cells after vaccination may be similar at different https://www.selleckchem.com/products/pexidartinib-plx3397.html ages; however, additional studies are required to confirm this. An interesting finding was that the peak response detected with the IFN-γ ELISpot assay was at 7 days post-vaccination, while the peak response detected with the whole blood intracellular cytokine staining assay was at 28 days post-vaccination in adolescents. We did not have whole blood samples at 28 days from children to perform the intracellular

cytokine staining assay. The ELISpot assay detects every IFN-γ-expressing cell present in PBMC, whereas the whole blood intracellular cytokine assay detects cytokine expression in the gated T-cell subsets. The latter analysis showed that CD8+ T cells did not contribute significantly to the Ag85A-specific response, and CD4–CD8– T-cell cytokine expression was not detected (data not shown); therefore, non-T cells, such as NK cells, may have contributed to the IFN-γ production detected by the ELISpot assay. This will require confirmation in future studies. Memory T cells can be classified into two major subsets based on CCR7 and CD45RA expression, so-called central memory cells (CCR7+CD45RA−) and effector memory cells (CCR7−CD45RA−). Central memory T cells have been hypothesized to be an optimal phenotype for long-lived protection after vaccination, even though evidence from vaccine studies is lacking 42, 43.