In our longitudinal analysis of HIV-TB co-infected individuals, we found that TB treatment (1) altered the functional profile of PPD-specific CD4 T-cells, specifically subsets producing MIP-1β and IL-2, (2) reduced the frequency of PPD-specific CD4 T-cells expressing an EM phenotype while simultaneously increasing the proportion with a CM phenotype, and (3) reduced expression of PD-1 and CTLA-4 on PPD-specific CD4 T-cells. The gene discussed is CTLA4; the disease is tuberculosis.