These results advance our understanding of CD4 T cell-mediated control of M. tuberculosis, establish CD4 T cell-derived GM-CSF as a potent bactericidal effector and, by uncovering a novel mechanism for HIF-1⍺ activation, emphasize the central importance of HIF-1⍺ for intracellular immunity to TB. The gene discussed is CSF2; the disease is tuberculosis.