title: Mycolic acid-specific T cells protect against Mycobacterium tuberculosis infection in a humanized transgenic mouse model.
abstract: Group 1 CD1 molecules, CD1a, CD1b and CD1c, present lipid antigens from Mycobacterium tuberculosis (Mtb) to T cells. Mtb lipid-specific group 1 CD1-restricted T cells have been detected in Mtb-infected individuals. However, their role in protective immunity against Mtb remains unclear due to the absence of group 1 CD1 expression in mice. To overcome the challenge, we generated mice that expressed human group 1 CD1 molecules (hCD1Tg) and a CD1b-restricted, mycolic-acid specific TCR (DN1Tg). Using DN1Tg/hCD1Tg mice, we found that activation of DN1 T cells was initiated in the mediastinal lymph nodes and showed faster kinetics compared to Mtb Ag85B-specific CD4(+) T cells after aerosol infection with Mtb. Additionally, activated DN1 T cells exhibited polyfunctional characteristics, accumulated in lung granulomas, and protected against Mtb infection. Therefore, our findings highlight the vaccination potential of targeting group 1 CD1-restricted lipid-specific T cells against Mtb infection.
authors.affiliation: Department of Microbiology and Immunology, Northwestern University, Chicago, United States.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Microbiology and Immunology, Northwestern University, Chicago, United States.
authors.forename: Sarah
authors.initials: S
authors.lastname: Siddiqui
authors.affiliation: Department of Microbiology and Immunology, Northwestern University, Chicago, United States.
authors.forename: Shaobin
authors.initials: S
authors.lastname: Shang
authors.affiliation: Department of Microbiology and Immunology, Northwestern University, Chicago, United States.
authors.forename: Yao
authors.initials: Y
authors.lastname: Bian
authors.affiliation: Department of Microbiology and Immunology, Northwestern University, Chicago, United States.
authors.forename: Sreya
authors.initials: S
authors.lastname: Bagchi
authors.affiliation: Department of Microbiology and Immunology, Northwestern University, Chicago, United States.
authors.forename: Ying
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Microbiology and Immunology, Northwestern University, Chicago, United States.
authors.forename: Chyung-Ru
authors.initials: CR
authors.lastname: Wang
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D018949:Antigens, CD1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009171:Mycolic Acids / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D018949:Antigens, CD1; D009171:Mycolic Acids; D011948:Receptors, Antigen, T-Cell
keywords: CD1; Mycobaterium tuberculosis; Mycolic acid; T lymphocytes; immunology; mouse