The presence of LAG-3 in nonhuman primates undergoing an active Mycobacterium tuberculosis infection (HEM4P.252)

Abstract

Abstract Th1 T cells are essential in the immune response against Mycobacterium tuberculosis (Mtb) infections. Lymphocyte activation gene-3 (LAG-3) regulates this response through the diminishment of effector T cells and the impairment of monocyte differentiation. We hypothesize that LAG-3 up-regulation within Mtb infected nonhuman primates (NHPs) will suppress the Th1 portion of the host immune response resulting in conditions that favor the pathogen and create active tuberculosis (TB) within the host. Here we are studying LAG-3 expression in rhesus macaques infected with aerosolized Mtb. We have chosen the macaque model due to their similarities to humans in the spectrum of TB disease, as well as the architecture of Mtb induced lung granulomas. Previous studies have implied that LAG-3 may have a role in the activation of Mtb infections. There is increasing evidence that up-regulation of LAG-3 occurs in the lungs of animals experiencing TB activation. Further investigation of the lung tissue of these infected animals with fluorescent immunohistochemistry visualized with confocal microscopy has illustrated LAG-3 to be largely present within the outer periphery of the lung. Cells expressing LAG-3 have shown to include T cells and NK cells, with large numbers of these cells appearing in close vicinity to certain populations of antigen presenting cells. These results show that in animals undergoing TB activation, LAG-3 has potential to play an immunomodulatory role in this process.