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.
Mucosal Immunology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Isabelle J
IJ
Suffia
Stacie K
SK
Reckling
Ciriaco A
CA
Piccirillo
Romina S
RS
Goldszmid
Yasmine
Y
Belkaid
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