MHC Class II Restricted Innate-Like Double Negative T Cells Contribute to Optimal Primary and Secondary Immunity to Leishmania major

PLoS Pathogens

Kanami Orihara¹  Ping Jia¹  Ifeoma Okwor¹  Zhirong Mou¹  Jude Ezeh Uzonna¹  Dong Liu¹ 

[1] Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada

关键词: T cells;    Cell-mediated immunity;    Parasitic diseases;    Cytotoxic T cells;    Flow cytometry;    Spleen;    Cytokines;    Major histocompatibility complex;   

DOI  :  10.1371/journal.ppat.1004396

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY