Single-cell profiling identifies T cell subsets associated with control of tuberculosis dissemination

Area of Science:

• Immunology
• T cell biology
• Tuberculosis research

Background:

• Tuberculosis (TB) remains a major global health challenge.
• Understanding the T cell immune response is crucial for developing effective TB control strategies.

Purpose of the Study:

• To identify specific T cell subsets associated with the control of tuberculosis.
• To investigate the role of different T cell populations in TB pathogenesis and dissemination.

Main Methods:

• Single-cell transcriptome and T cell receptor sequencing were employed on T cells from TB patients and healthy controls.
• Unbiased Uniform Manifold Approximation and Projection (UMAP) clustering was used to identify distinct T cell subsets.
• Quantitative analysis of specific T cell populations and their correlation with disease extent.

Main Results:

• Fourteen distinct T cell subsets were identified.
• A cluster of Granzyme K (GZMK)-expressing CD8+ cytotoxic T cells and a SOX4-expressing CD4+ central memory T cell cluster were found to be depleted in TB patients.
• A MKI67-expressing proliferating CD3+ T cell cluster was expanded in TB patients.
• The ratio of Granzyme K-expressing CD8+CD161-Ki-67- and CD8+Ki-67+ T cells was significantly reduced and inversely correlated with TB lesion extent.
• Ratios of Granzyme B-expressing CD8+Ki-67+ and CD4+CD161+Ki-67- T cells, and Granzyme A-expressing CD4+CD161+Ki-67- T cells, correlated with TB lesion extent.

Conclusions:

• Granzyme K-expressing CD8+ T cell subsets may play a protective role against tuberculosis dissemination.
• Specific T cell subset alterations, particularly the depletion of GZMK+ CD8+ T cells, are associated with TB.
• Further research into these T cell subsets could inform novel therapeutic approaches for tuberculosis.