ICOS and Bcl6-dependent pathways maintain a CD4 T cell population with memory-like properties during tuberculosis.
Bottom Line: When transferred into uninfected animals, these cells persist, mount a robust recall response, and provide superior protection to Mtb rechallenge when compared to terminally differentiated Th1 cells that reside preferentially in the lung-associated vasculature.Thus, the molecular pathways required to maintain Mtb-specific CD4 T cells during ongoing infection are similar to those that maintain memory CD4 T cells in scenarios of antigen deprivation.These results suggest that vaccination strategies targeting the ICOS and Bcl6 pathways in CD4 T cells may provide new avenues to prevent TB.
Affiliation: Seattle Biomedical Research Institute (renamed Center for Infectious Disease Research), Seattle, WA 98109 Department of Immunology, University of Washington School of Medicine, Seattle, WA 98104.Show MeSH
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Mentions: We detected IFN-γ in ESAT-6 tetramer-binding and CD44hi (but not CD44low) CD4 T cells (Fig. 2 A) using intracellular cytokine staining of T cells directly ex vivo without in vitro restimulation (Shafiani et al., 2013). At 16 d after infection, ~20% of ESAT-6–specific T cells recovered from the lungs produced IFN-γ, and this percentage gradually increased to ~40% on day 300 (Fig. 2 B). IFN-γ production was dependent on TCR signaling in at least half of these cells because administration of cyclosporine A (CsA; an inhibitor of proximal TCR-mediated signaling; Schreiber and Crabtree, 1992), 4 h before euthanasia blocked IFN-γ production in ~50% of the cells (Fig. 2 C). Collectively, our results indicate that ESAT-6 antigen is readily available for T cell recognition throughout infection and high numbers of ESAT-6–specific T cells are maintained in the lung in the presence of chronic antigenic stimulation.
Affiliation: Seattle Biomedical Research Institute (renamed Center for Infectious Disease Research), Seattle, WA 98109 Department of Immunology, University of Washington School of Medicine, Seattle, WA 98104.