MHC class II restricted innate-like double negative T cells contribute to optimal primary and secondary immunity to...

Area of Science:

• Immunology
• Parasitology
• Cellular Biology

Background:

• CD4(+) T cells are traditionally considered key in anti-Leishmania immunity.
• Emerging evidence suggests double negative (DN) T cells (CD3(+)CD4(-)CD8(-)) may play a significant role.
• The role of DN T cells in secondary anti-Leishmania immunity remains under-investigated.

Purpose of the Study:

• To investigate the function and importance of DN T cells in primary and secondary anti-Leishmania immunity.
• To determine if DN T cells possess memory-like characteristics against Leishmania.
• To elucidate the contribution of DN T cells to protective immunity in experimental cutaneous leishmaniasis.

Main Methods:

• Analysis of DN T cell proliferation and cytokine production (IFN-γ, TNF, IL-17) in infected mice.
• Assessment of granzyme B (GrzB) expression in DN T cells.
• In vitro and in vivo functional assays following L. major challenge.
• Characterization of DN T cell receptor (TCR) type, specificity, and MHC restriction.
• In vivo depletion and adoptive transfer studies to assess immune contribution.

Main Results:

• DN T cells extensively proliferate and produce effector cytokines (IFN-γ, TNF, IL-17) and GrzB during primary and secondary L. major infections.
• DN T cells from healed mice exhibit rapid proliferation and cytokine production upon rechallenge, indicating memory-like properties.
• DN T cells are predominantly αβ TCR expressing, Leishmania-specific, and MHC class II-restricted, with an innate-like gene profile.
• Depletion and transfer studies confirm DN T cells' contribution to optimal primary and secondary anti-Leishmania immunity.

Conclusions:

• DN T cells are critical effectors in both primary and secondary anti-Leishmania immunity.
• DN T cells display memory-like functions, contributing to protective immunity against L. major.
• These findings establish DN T cells as key players in experimental cutaneous leishmaniasis, challenging the traditional view focused solely on CD4(+) T cells.