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Identification of Rare Antigen-Specific T Cells from Mouse Lungs with Peptide:Major Histocompatibility Complex Tetramers
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Phenotypical and functional analysis of memory and effector human CD8 T cells specific for mycobacterial antigens

Nadia Caccamo1, Serena Meraviglia, Carmela La Mendola

  • 1Dipartimento di Biopatologia e Metodologie Biomediche, Università di Palermo, Palermo, Italy.

Journal of Immunology (Baltimore, Md. : 1950)
|July 20, 2006
PubMed

Insights

Tuberculosis (TB) patients show low levels of Ag85A-specific CD8 T cells before treatment. Therapy restores these immune cells, improving function and phenotype, crucial for understanding protective immune responses against TB.

Area of Science:

  • Immunology
  • Infectious Diseases
  • Microbiology

Background:

  • Tuberculosis (TB) remains a global health crisis, infecting a third of the world's population.
  • Memory CD8 T cells display significant heterogeneity, impacting their role in infectious diseases.
  • Understanding Ag85A-specific CD8 T cell responses is vital for developing effective TB vaccines.

Purpose of the Study:

  • To investigate the frequency, phenotype, and function of Ag85A epitope-specific HLA-A*0201 CD8 T cells in children with TB.
  • To compare immune cell profiles before and after chemotherapy in TB patients versus healthy contacts.
  • To explore CD8 T cell compartmentalization in tuberculous meningitis.

Main Methods:

  • Utilized Ag85A peptide/HLA-A*0201 pentamer technology to identify specific CD8 T cells.
  • Performed ex vivo analysis of CD45RA and CCR7 surface markers to assess T cell phenotypes.
  • Measured IFN-gamma production and perforin expression in pentamer-specific CD8 T cells.

Main Results:

  • Tuberculous children had low frequencies of blood Ag85A-specific CD8 T cells, which increased to healthy contact levels post-therapy.
  • Active TB showed a skewed CD8 T cell profile (more central memory, fewer terminally differentiated cells), normalized after treatment.
  • Patients had reduced IFN-gamma and perforin production by CD8 T cells, recovering post-therapy.
  • Elevated effector/terminally differentiated CD8 T cells in CSF suggest disease site compartmentalization in meningitis.

Conclusions:

  • Chemotherapy restores Ag85A-specific CD8 T cell frequency, phenotype, and function in children with TB.
  • CD8 T cell responses are compartmentalized at the disease site in tuberculous meningitis.
  • Characterizing Ag-specific CD8 T cells provides insights for designing protective TB vaccines.

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