Characterization of CD4 and CD8 T cells producing IFN-γ in human latent and active tuberculosis

Summary Patients with pulmonary tuberculosis (PTB) frequently have reduced IFN-γ production in response to mycobacterial antigens, compared to individuals with latent Mycobacterium tuberculosis infection (LTBi). However, it is not clear whether this reduced responsiveness is restricted to a particular T cell subset. Herein, PBMCs from 26 PTB patients, 30 household contacts (HHCs) of PTB, and 30 tuberculin positive (TST+) healthy subjects not recently exposed to PTB, were stained with CFSE and stimulated non-specific (PPD) for 120 h, and specific (CFP-10/ESAT-6) and latency (HSpX) mycobacterial antigens for 144 h and the percentage of CD4 + and CD8 + IFN-γ + T cells responding determined by flow cytometry, in addition to their memory phenotype by the CD45RO and CD27 expression. PTB had decreased frequency of both CD4 + and CD8 + precursor cells, as well as decreased number of CD4 + IFN-γ + cells in response to all antigens, whereas CD8 + IFN-γ + cells were decreased in response to PPD and ESAT-6, but not to CFP-10 and HSpX. HHCs exhibited the highest precursor frequencies and IFN-γ responses, irrespective of the antigen employed. The CD4 + /CD8 + cell ratios showed that in response to PPD CD4 + precursor and IFN-γ-producer cells are more frequent than their CD8 + counterparts, and that PTB have a decreased CD4 + IFN-γ + /CD8 + IFN-γ + ratio in response to PPD, CFP-10, and ESAT-6. CD4 + IFN-γ + and CD8 + IFN-γ + cells exhibited a central memory phenotype (CD45RO + CD27 + ), irrespective of the group of subjects and the antigen used for stimulation. In conclusion, PTB patients had a decreased percentage of CD4 + and CD8 + precursor cells and CD4 + IFN-γ + . HHCs exhibited the highest frequency of CD4 + and CD8 + precursors and CD4 + IFN-γ + -producing cells.