Abstract
Tissue-resident memory T cells are required for establishing protective immunity against a variety of different pathogens, although the mechanisms mediating protection by CD4+ resident memory T cells are still being defined. In this study we addressed this issue with a population of protective skin-resident, IFNγ-producing CD4+ memory T cells generated following Leishmania major infection. We previously found that resident memory T cells recruit circulating effector T cells to enhance immunity. Here we show that resident memory CD4+ T cells mediate the delayed-hypersensitivity response observed in immune mice and provide protection without circulating T cells. This protection occurs rapidly after challenge, and requires the recruitment and activation of inflammatory monocytes, which limit parasites by production of both reactive oxygen species and nitric oxide. Overall, these data highlight a novel role for tissue-resident memory cells in recruiting and activating inflammatory monocytes, and underscore the central role that skin-resident T cells play in immunity to cutaneous leishmaniasis.
Highlights
Tissue-resident memory T cells (TRM) are critical mediators of immunity against a number of different infections in a variety of different tissues [1,2,3,4,5,6,7,8,9,10,11]
We previously discovered that a population of skin-resident memory CD4+ T cells that develop in immune mice enhances the protective immune response against leishmania parasites
This protection was dependent upon the recruitment of inflammatory monocytes to the challenge site, which reduced the parasite burden in a nitric oxide and reactive oxygen species dependent manner
Summary
Tissue-resident memory T cells (TRM) are critical mediators of immunity against a number of different infections in a variety of different tissues [1,2,3,4,5,6,7,8,9,10,11]. Similar to some forms of human cutaneous leishmaniasis, C57BL/6 mice infected with Leishmania major develop lesions that heal over several weeks, and once resolved the mice exhibit immunity to reinfection [19]. Studies in this model have shown that in a primary leishmania infection, innate cells including neutrophils, monocytes, and dendritic cells are rapidly recruited to the site of challenge [20,21,22,23]. Given their location at the site of a challenge infection and their rapid production of IFNγ, it might be expected that CD4+ TRM cells may provide some level of rapid protection that is independent of additional T cell recruitment from the blood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: 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.
