Mycobacterium tuberculosis-specific CD8+ T cells are functionally and phenotypically different between latent...

Area of Science:

• Immunology
• Infectious Diseases
• Microbiology

Background:

• Protective immunity against Mycobacterium tuberculosis (Mtb) is not fully understood.
• The specific role of Mtb-specific CD8(+) T cells in tuberculosis (TB) immunity is debated.

Purpose of the Study:

• To comprehensively characterize Mtb-specific CD8(+) T cells in individuals with latent TB infection (LTBI) and active TB disease.
• To investigate the phenotypic and functional differences of these T cells in relation to disease state and clinical presentation.

Main Methods:

• Phenotypic and functional analysis of Mtb-specific CD8(+) T cells in 326 subjects (LTBI and TB).
• Flow cytometry was used to assess cell surface markers, cytokine profiles, and cytotoxic potential.
• In vitro expansion was performed to evaluate functional capacity.

Main Results:

• Mtb-specific CD8(+) T cells were found in 60% of TB patients and 15% of LTBI subjects, with similar magnitudes.
• LTBI subjects had T EMRA cells, while TB patients had TEM cells, with distinct co-expression patterns of 2B4, CD160, and PD-1.
• Cytokine profiles were similar, but cytotoxic molecules like perforin and granulysin were expressed upon in vitro expansion. Responses were less frequent and proliferation greater in extrapulmonary TB.

Conclusions:

• The activity of Mtb infection and clinical presentation are linked to distinct Mtb-specific CD8(+) T-cell profiles.
• These findings enhance our understanding of the complex interaction between Mtb and the host immune system.
• Characterizing these T cells may offer new avenues for diagnosing and managing TB.