The immunoregulatory molecule PD-1 and cyclophilin D (CypD)-mediated T cell metabolism promote host resistance to TB, with checkpoint inhibitors (PD-1 blockade) and CypD genetic blockade exacerbating TB disease and immunopathology via overproduction of IFN-γ and TNF-α from CD4+ T cells, and elevate infiltrates of pro-inflammatory CD8+ T cells.69 This evidence concerns the gene CD4 and tuberculosis.