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

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. © 2014 mou et al.