Immune Netw.  2003 Sep;3(3):235-241. 10.4110/in.2003.3.3.235.

The Study of MHC class I Restricted CD8+ T Cell Mediated Immune Responses against Mycobacterium tuberculosis Infection: Evidence of M. tuberculosis Specific CD8+ T Cells in TB Patients and PPD+ Healthy Individuals

Affiliations
  • 1Department of Microbiology, Brain Korea 21 Project for Medical Sciences, Yonsei University Medical Center, Korea. scho@yumc.yonsei.ac.kr
  • 2Hallym Institution for Genome Application Hallym University, Korea.
  • 3National Masan Tuberculosis Hospital, 4Department of Internal Medicine, Ewha Womans University Tongdaemun Hospital, Korea.

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-gammaelispot 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 1.7x10(5) PBMC based on ex vivo IFN-gamma 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-gamma 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-gamma 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.

Keyword

Mycobacterium tuberculosis; CD8+ T cells; peptide epitopes; HLA-A*0201; IFN-gamma elispot assay

MeSH Terms

Cell Line
Enzyme-Linked Immunospot Assay
Epitopes
HLA-A2 Antigen
Humans
Mycobacterium tuberculosis*
Mycobacterium*
Peptides
T-Lymphocytes*
Tissue Donors
Tuberculosis*
Epitopes
HLA-A2 Antigen
Peptides
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