title: IL-2 simultaneously expands Foxp3+ T regulatory and T effector cells and confers resistance to severe tuberculosis (TB): implicative Treg-T effector cooperation in immunity to TB.
abstract: The possibility that simultaneous expansion of T regulatory cells (Treg) and T effector cells early postinfection can confer some immunological benefits has not been studied. In this study, we tested the hypothesis that early, simultaneous cytokine expansion of Treg and T effector cells in a tissue infection site can allow these T cell populations to act in concert to control tissue inflammation/damage while containing infection. IL-2 treatments early after Mycobacterium tuberculosis infection of macaques induced simultaneous expansion of CD4(+)CD25(+)Foxp3(+) Treg, CD8(+)CD25(+)Foxp3(+) T cells, and CD4(+) T effector/CD8(+) T effector/Vγ2Vδ2 T effector populations producing anti-M. tuberculosis cytokines IFN-γ and perforin, and conferred resistance to severe TB inflammation and lesions. IL-2-expanded Foxp3(+) Treg readily accumulated in pulmonary compartment, but despite this, rapid pulmonary trafficking/accumulation of IL-2-activated T effector populations still occurred. Such simultaneous recruitments of IL-2-expanded Treg and T effector populations to pulmonary compartment during M. tuberculosis infection correlated with IL-2-induced resistance to TB lesions without causing Treg-associated increases in M. tuberculosis burdens. In vivo depletion of IL-2-expanded CD4(+)Foxp3(+) Treg and CD4(+) T effectors during IL-2 treatment of M. tuberculosis-infected macaques significantly reduced IL-2-induced resistance to TB lesions, suggesting that IL-2-expanded CD4(+) T effector cells and Treg contributed to anti-TB immunity. Thus, IL-2 can simultaneously activate and expand T effector cells and Foxp3(+) Treg populations and confer resistance to severe TB without enhancing M. tuberculosis infection.
authors.affiliation: Department of Microbiology and Immunology, Center for Primate Biomedical Research, College of Medicine, University of Illinois, Chicago, IL 60612, USA.
authors.forename: Crystal Y
authors.initials: CY
authors.lastname: Chen
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.forename: Shuyu
authors.initials: S
authors.lastname: Yao
authors.forename: Lisa
authors.initials: L
authors.lastname: Halliday
authors.forename: Gucheng
authors.initials: G
authors.lastname: Zeng
authors.forename: Richard C
authors.initials: RC
authors.lastname: Wang
authors.forename: Zheng W
authors.initials: ZW
authors.lastname: Chen
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000276:immunology; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology*; D008252:Macaca fascicularis; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D054353:Perforin / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology*
chemical_list: D051858:Forkhead Transcription Factors; D007376:Interleukin-2; D054353:Perforin; D007371:Interferon-gamma