title: Pathogen-related differences in the abundance of presented antigen are reflected in CD4+ T cell dynamic behavior and effector function in the lung.
abstract: Exposure to pathogens in the periphery elicits effector T cell differentiation in local lymph nodes followed by migration of activated T cells to and within the infected site. However, the relationships among pathogen abundance, Ag display on MHC molecules, effector T cell dynamics, and functional responses at the infected sites are incompletely characterized. In this study, we compared CD4(+) T cell effector dynamics and responses during pulmonary mycobacterial infection versus acute influenza infection. Two-photon imaging together with in situ as well as ex vivo analysis of cytokine production revealed that the proportion of migration-arrested, cytokine-producing effector T cells was dramatically higher in the influenza-infected lungs due to substantial differences in Ag abundance in the two infectious states. Despite the marked inflammatory conditions associated with influenza infection, histocytometric analysis showed that cytokine production was focal, with a restriction to areas of significant Ag burden. Optimal effector function is thus constrained by the availability of TCR ligands, pointing to the value of increasing Ag stimulation rather than effector numbers in harnessing CD4(+) T cells for therapeutic purposes in such conditions.
authors.affiliation: Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.|Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Parizad
authors.initials: P
authors.lastname: Torabi-Parizi
authors.affiliation: Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Nienke
authors.initials: N
authors.lastname: Vrisekoop
authors.affiliation: Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kastenmuller
authors.affiliation: Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Gerner
authors.affiliation: Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Jackson G
authors.initials: JG
authors.lastname: Egen
authors.affiliation: Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Germain
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D008099:Liver / Q000276:immunology; D008168:Lung / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology; D009975:Orthomyxoviridae / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma