title: Cutting edge: control of Mycobacterium tuberculosis infection by a subset of lung parenchyma-homing CD4 T cells.
abstract: Th1 cells are critical for containment of Mycobacterium tuberculosis infection, but little else is known about the properties of protective CD4 T cell responses. In this study, we show that the pulmonary Th1 response against M. tuberculosis is composed of two populations that are either CXCR3(hi) and localize to lung parenchyma or are CX3CR1(hi)KLRG1(hi) and are retained within lung blood vasculature. M. tuberculosis-specific parenchymal CD4 T cells migrate rapidly back into the lung parenchyma upon adoptive transfer, whereas the intravascular effectors produce the highest levels of IFN-γ in vivo. Importantly, parenchymal T cells displayed greater control of infection compared with the intravascular counterparts upon transfer into susceptible T cell-deficient hosts. Thus, we identified a subset of naturally generated M. tuberculosis-specific CD4 T cells with enhanced protective capacity and showed that control of M. tuberculosis correlates with the ability of CD4 T cells to efficiently enter the lung parenchyma rather than produce high levels of IFN-γ.
authors.affiliation: T Lymphocyte Biology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Sakai
authors.forename: Keith D
authors.initials: KD
authors.lastname: Kauffman
authors.forename: Jason M
authors.initials: JM
authors.lastname: Schenkel
authors.forename: Cortez C
authors.initials: CC
authors.lastname: McBerry
authors.forename: Katrin D
authors.initials: KD
authors.lastname: Mayer-Barber
authors.forename: David
authors.initials: D
authors.lastname: Masopust
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Barber
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001808:Blood Vessels / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D000073883:CX3C Chemokine Receptor 1; D002465:Cell Movement / Q000276:immunology; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000502:physiology; D054367:Receptors, CXCR3 / Q000276:immunology / Q000378:metabolism; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology
chemical_list: D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; C515188:Cxcr3 protein, mouse; C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D011971:Receptors, Immunologic; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens