CD4+ T cells recruit, then engage macrophages in cognate interactions to clear Mycobacterium tuberculosis from the lungs.

IFN-{gamma}-producing CD4+ T cells are required for protection against lethal Mycobacterium tuberculosis (Mtb) infections. However, the ability of CD4+ T cells to suppress Mtb growth cannot be fully explained by IFN-{gamma} or other known T cell products. In this study, we show that CD4+ T cell-derived IFN-{gamma} promoted the recruitment of monocyte-derived macrophages (MDMs) to the lungs of Mtb-infected mice. Although the recruited MDMs became quickly and preferentially infected with Mtb, CD4+ T cells rapidly disinfected the MDMs. Clearance of Mtb from MDMs was not explained by IFN-{gamma}, but rather by MHCII-mediated cognate interactions with CD4+ T cells. These interactions promoted MDM expression of glycolysis genes essential for Mtb control. Thus, by recruiting MDMs, CD4+ T cells initiate a cycle of bacterial phagocytosis, Mtb antigen presentation and disinfection in an attempt to clear the bacteria from the lungs.