Infected site-restricted Foxp3+ natural regulatory T cells are specific for microbial antigens.
Natural regulatory T (T reg) cells are involved in control of the immune response, including response to pathogens. Previous work has demonstrated that the repertoire of natural T reg cells may be biased toward self-antigen recognition. Whether they also recognize foreign antigens and how this recognition contributes to their function remain unknown. Our studies addressed the antigenic specificity of natural T reg cells that accumulate at sites of chronic infection with Leishmania major in mice. Our results support the idea that natural T reg cells are able to respond specifically to foreign antigens in that they strongly proliferate in response to Leishmania-infected dendritic cells, they maintain Foxp3 expression, and Leishmania-specific T reg cell lines can be generated from infected mice. Surprisingly, the majority of natural T reg cells at the infected site are Leishmania specific. Further, we showed that parasite-specific natural T reg cells are restricted to sites of infection and that their survival is strictly dependent on parasite persistence.
Suffia
Isabelle J
IJ
Mucosal Immunology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Reckling
Stacie K
SK
Piccirillo
Ciriaco A
CA
Goldszmid
Romina S
RS
Belkaid
Yasmine
Y
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation; D002908:Chronic Disease; D003713:Dendritic Cells / Q000276:immunology* / Q000469:parasitology; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D013045:Species Specificity; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000469:parasitology
D000953:Antigens, Protozoan; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse