Multifunctional CD4(+) T cells correlate with active Mycobacterium tuberculosis infection

Area of Science:

• Immunology
• Infectious Diseases
• T-cell Biology

Background:

• Th1 CD4(+) T cells and their cytokines are vital for controlling Mycobacterium tuberculosis infection.
• Understanding the functional states of CD4(+) T cells is crucial for differentiating latent tuberculosis infection (LTBI) from active tuberculosis (TB).

Purpose of the Study:

• To evaluate the distribution of distinct functional states of CD4(+) T cells in individuals with LTBI and active TB.
• To identify potential immunological correlates of protection and therapeutic monitoring for tuberculosis.

Main Methods:

• Multiparametric flow cytometry was used to analyze seven functional states of CD4(+) T cells.
• The study compared T-cell profiles between LTBI and active TB patients, and monitored changes after anti-mycobacterial therapy.

Main Results:

• Triple cytokine-expressing CD4(+) T cells (IFN-γ/IL-2/TNF-α) were significantly more prevalent in active TB patients (85-90%) compared to LTBI subjects (10-15%).
• LTBI subjects exhibited a 12- to 15-fold higher proportion of IL-2/IFN-γ double expressors and IFN-γ single expressors.
• The frequency of multifunctional T cells decreased in TB patients after therapy, correlating with bacterial load.

Conclusions:

• Distinct IFN-γ, IL-2, and TNF-α expression profiles in M. tuberculosis-specific CD4(+) T cells differentiate active TB from LTBI.
• These T-cell signatures may serve as biomarkers for protective immunity and effective anti-mycobacterial treatment monitoring.