Effector function prior to establishment of the pathogen niche is required for protective CD4+ T cell-mediated immunity
AdvisorPeters, Nathan C
AuthorHohman, Leah Shan
Committee MemberFinney, Constance
CD4+ T cells
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AbstractCD4+ T helper 1 effector cells (Th1EFF) are critical for protective immunity against pathogens that employ phagocytic cells as hosts for replication and persistence. Despite this knowledge, the degree to which protective Th1EFF cells are reliant on the time at which they interact with infected phagocytic cells to mediate their protective effect is not fully understood. Employing the Leishmania major model organism of phagocyte infection, we report that Th1 TEFF cells must deliver effector function during an acute window post-challenge in order to mediate protection. Rapid CD4 + Th1 effector function was required for Th1EFF cells to capitalize on an early activation window in order to prevent the establishment of a pathogen niche, as evidenced by altered recruitment, gene expression and functional capacity of both innate and adaptive immune cells. Delayed Th1EFF availability was unable to overcome parasite niche establishment and mediate efficient protection, even when Leishmania-antigen specific Th1 cells were provided in large quantities. Thus, we propose that rapid effector function mediated by circulating TEFF cells is required to prevent phagosomal pathogen-mediated immunomodulation of host phagocytes and represents an important consideration for prophylactic vaccination against phagosomal pathogens that requires Th1 immunity.
CitationHohman, L. S. (2021). Effector function prior to establishment of the pathogen niche is required for protective CD4+ T cell-mediated immunity (Unpublished doctoral thesis). University of Calgary, Calgary, AB.
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