Abstract
Although it is generally believed that CD4+ T cells play important roles in anti-Leishmania immunity, some studies suggest that they may be dispensable, and that MHC II-restricted CD3+CD4−CD8− (double negative, DN) T cells may be more important in regulating primary anti-Leishmania immunity. In addition, while there are reports of increased numbers of DN T cells in Leishmania-infected patients, dogs and mice, concrete evidence implicating these cells in secondary anti-Leishmania immunity has not yet been documented. Here, we report that DN T cells extensively proliferate and produce effector cytokines (IFN-γ, TNF and IL-17) and granzyme B (GrzB) in the draining lymph nodes and spleens of mice following primary and secondary L. major infections. DN T cells from healed mice display functional characteristics of protective anti-Leishmania memory-like cells: rapid and extensive proliferation and effector cytokines production following L. major challenge in vitro and in vivo. DN T cells express predominantly (> 95%) alpha-beta T cell receptor (αβ TCR), are Leishmania-specific, restricted mostly by MHC class II molecules and display transcriptional profile of innate-like genes. Using in vivo depletion and adoptive transfer studies, we show that DN T cells contribute to optimal primary and secondary anti-Leishmania immunity in mice. These results directly identify DN T cells as important players in effective and protective primary and secondary anti-L. major immunity in experimental cutaneous leishmaniasis.
Highlights
The spectrum of disease collectively called Leishmaniasis is caused by several species of protozoan parasites belonging to the genus Leishmania
It is generally believed that CD4+ T cells mediate anti-Leishmania immunity, some studies suggest that CD3+CD42CD82 T cells may play a more important role in regulating primary anti-Leishmania immunity
We report that DN T cells extensively proliferate and produce effector cytokines in mice following primary and secondary L. major infections
Summary
Several studies have reported increased numbers of DN T cells in blood of Leishmania-infected patients [11,12], dogs [13], and in spleens of Leishmania-infected mice [14] These cells have been proposed to contribute to primary and vaccine-induced immunity against Leishmania. We report for the first time, that infection with L. major leads to activation and proliferation of DN T cells in the draining lymph nodes (dLNs) and spleens of infected mice. These cells produce effector cytokines (IFN-c and TNF), display functional characteristics of memory-like cells and contribute to optimal primary and secondary protection against L. major infection
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.