Furthermore, the expression of all the checkpoint molecules was found to be significantly higher across both CD4+ and CD8+ T cells in HIV-TB co-infected individuals as compared to healthy controls, while the frequencies of both CD4+ as well as CD8+ T cells expressing ICMs like TIGIT, CTLA-4 and PD-1 and CD4+ T cells expressing TIM-3 and LAG-3 were significantly increased in HIV-TB co-infected individuals as compared to TB mono-infected individuals, indicating an enhanced level of immune-exhaustion in HIV-TB co-infected hosts as compared to HIV or Mtb mono-infected ones. This evidence concerns the gene CD4 and tuberculosis.