MHC class I 분자들에 의해 제시되는 Epitope을 인지하는 CD8+ T 림프구의 결핵균 감염에 대한 면역반응의 연구: 결핵 환자와 PPD+ 건강개체에 존재하는 결핵균 항원에 특정한 CD8+ T세포

Abstract

Background: 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 (ThyA30-38, RpoB127-135, 85B15-23, PstA175-83). In this study, we investigated the immune responses induced by these peptide specific CD8+ T cells in latently and chronically infected people with TB.

Methods: 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.

Results: 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 PstA175-83 specific CD8+ T cell population in PPD+ healthy donors is heterogeneous since approximately 25～33% of PstA175-83 specific CD8+ T cell population in PPD+ healthy donors produced IFN-γ upon peptide stimulation.

Conclusion: 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.