XCL1 (lymphotactin) chemokine produced by activated CD8 T cells during the chronic stage of infection with Mycobacterium tuberculosis negatively affects production of IFN-gamma by CD4 T cells and participates in granuloma stability

Abstract

CD8 T cell immune responses are known not to be essential during the initial stages of infection with Mycobacterium tuberculosis (Mtb), but their presence becomes important as the chronic infection ensues. The basis of this is still not clear. In previous studies, we showed that CD8 T cells have a distinctive positioning in the architecture of the granuloma lesion, with further changes throughout the course of the chronic infection. We have also hypothesized that further movement of lymphocytes once they are within the lung lesions could be associated with the levels of expression of the chemokine XCL1 (lymphotactin). XCL1 is produced mainly by activated CD8 T cells, and its chemotactic activity seems primarily controlling movement of CD4 and CD8 T cells. In this study, using a murine low-dose aerosol infection model coupled with antibody depletion of T cell subsets, we investigated the role of CD8 T cells in the control of the bacterial growth and in the pathogenesis of the disease in mice at early, mid, or late stages of the chronic disease state. Additionally, we also describe for the first time that during Mtb infection, activated CD8 T cells in the lungs produce XCL1 and that this chemokine is capable of controlling IFN-gamma production by CD4 T cells.