Involvement of different CD4(+) T cell subsets producing granzyme B in the immune response to Leishmania major...

Area of Science:

• Immunology
• Parasitology
• Cellular Biology

Background:

• Leishmania major (Lm) causes zoonotic cutaneous leishmaniasis (ZCL).
• Understanding the immune response to Lm excreted/secreted proteins (LmES) is crucial for vaccine development.
• Previous studies have not fully elucidated the effector cells involved in LmES immunogenicity.

Purpose of the Study:

• To investigate the immunogenicity of LmES in individuals healed from ZCL (HZCL).
• To identify the effector T cell populations responding to LmES.
• To explore the role of regulatory T cells (Tregs) in the immune response to LmES.

Main Methods:

• Peripheral blood mononuclear cells (PBMCs) from HZCL individuals and healthy controls (HC) were stimulated with LmES.
• Cell proliferation, cytokine (IFN-γ) production, and Granzyme B (GrB) expression were measured.
• Flow cytometry was used to identify T cell subsets, including Tregs (CD4(+)CD25(+)CD127(dim/-)).

Main Results:

• PBMCs from HZCL individuals showed significant proliferation and produced high levels of IFN-γ and GrB upon LmES stimulation.
• Both CD4(+) T cells and Tregs (CD4(+)CD25(+)CD127(dim/-)) produced IFN-γ and GrB in response to LmES.
• LmES were as effective as soluble Leishmania antigens in inducing immune responses.

Conclusions:

• LmES are immunogenic in humans, triggering a robust T cell response.
• CD4(+) T cells, encompassing both activated and regulatory subsets, play a key role in the immune response to LmES.
• These findings have implications for understanding leishmaniasis pathogenesis and developing Lm-based vaccines.