T-cell regulation in lepromatous leprosy

Area of Science:

• Immunology
• Microbiology
• Dermatology

Background:

• Regulatory T (Treg) cells maintain self-tolerance but can prolong pathogen survival in chronic infections.
• Lepromatous leprosy (LL) patients exhibit impaired T helper 1 (Th1) responses to Mycobacterium leprae despite strong humoral immunity.
• Understanding Treg cell function in LL is crucial for developing effective immunotherapies.

Purpose of the Study:

• To investigate the role of CD25+ Treg cells in Mycobacterium leprae-specific T-cell unresponsiveness in lepromatous leprosy (LL) patients.
• To analyze the impact of Treg cell depletion on IFN-γ responses to M. leprae in LL patients.
• To correlate Treg cell populations and markers in peripheral blood and skin lesions with disease presentation.

Main Methods:

• Peripheral blood mononuclear cells (PBMC) from LL patients were analyzed for IFN-γ responses to M. leprae before and after CD25+ cell depletion.
• Cell subset analysis of PBMC and immunohistochemistry of skin lesions were performed.
• Responses were compared between LL patients, treated LL patients, borderline tuberculoid leprosy (BT) patients, and healthy controls.

Main Results:

• Depletion of CD25+ cells restored M. leprae-specific IFN-γ responses in 38.8% of LL patients, which was reversible upon addition of autologous CD25+ cells.
• 61.1% of LL patients remained unresponsive even after CD25+ cell depletion.
• Increased numbers of FoxP3+ CD8+CD25+ T-cells were observed in LL patients compared to BT patients, and elevated CD68+CD163+ and FoxP3+ cells were found in LL skin lesions.

Conclusions:

• CD25+ regulatory T cells play a significant role in mediating M. leprae-specific Th1 unresponsiveness in lepromatous leprosy.
• These findings highlight the potential of targeting Treg cells for immunotherapeutic strategies in LL.
• The study identifies distinct Treg cell profiles in LL, contributing to the understanding of leprosy pathogenesis.