The protective immunity against tuberculosis (TB) involves both CD4+ T cells and CD8+ T cells. In our previous study, we defined four Mycobacterium tuberculosis derived peptide epitopes specific for HLA-A^*0201 restricted CD8+ T cells (ThyA_30-38, RpoB_127-135, 85B_15-23, PstA1_75-83). In this study, we investigated the immune responses induced by these peptide specific CD8+ T cells in latently and chronically infected people with TB.

We characterized these peptide specific CD8+ T cell population present in PBMC of both TB patients and PPD+healthy people using IFN-γelispot assay, intracellular staining and HLA-A2 dimer staining.

The frequency of peptide specific CD8+ T cell was in the range of 1 to 25 in 1.7×10⁵ PBMC based on ex vivo IFN-γ elispot assay, demonstrating that these peptide specific CD8+ T cell responses are induced in both TB patients and PPD+ people. Short term cell lines (STCL) specific for these peptides proliferated in vitro and secreted IFN-γ upon antigenic stimulation in PPD+ donors. Lastly, HLA-A^*0201 dimer assays indicated that PstA1_75-83 specific CD8+ T cell population in PPD+ healthy donors is heterogeneous since approximately 25~33% of PstA1_75-83 specific CD8+ T cell population in PPD+ healthy donors produced IFN-γ upon peptide stimulation.

Our results suggest that MHC class I restricted CD8+ T cell mediated immune responses to M. tuberculosis infection are induced in both TB patients and PPD + people; however, the CD8+ T cell population is functionally heterogeneous.