This disclosure relates to methods of treating and diagnosing a tuberculosis infection as pulmonary active or latent based on biomarkers expressed on pools of CD4+ cells. In certain embodiments, the disclosure relates to methods of treatment of a subject diagnosed with tuberculosis comprising the steps of, measuring a pool of CD4 IFN-γ cells for cells that also express CD38, HLA-DR, and/or Ki-67 providing a measurement; associating an increased measurement of CD4 IFN-γ cells that also express CD38, HLA-DR, Ki-67, compared to a control, as an indication that the subject has active tuberculosis; and treating the subject with an aggressive tuberculosis treatment.