title: Neonatal lung immune responses show a shift of cytokines and transcription factors toward Th2 and a deficit in conventional and plasmacytoid dendritic cells.
abstract: The high incidence of lung-damaging life-threatening respiratory infections in infants may be related to the immaturity of their immune systems. To determine whether lung immune features differ in early life compared with those in adulthood, whole lung as well as lung T lymphocyte and DC responses were investigated in BALB/c neonates versus adults. Higher expression of GATA-3 and rapid and sustained production of type 2 cytokines by lung explants after in vitro exposure to anti-CD3 was the hallmark of the neonatal period, suggestive of a Th2 bias. Neonatal lung GATA-3-producing cells were identified as CD3(+), CD4 and CD8 double-negative T lymphocytes, a subset found at a higher frequency in neonatal than adult lung. The neonatal lungs contained fewer conventional DCs, with a lower ratio of CD103(+) to CD11b(+) DCs, and a much lower number of plasmacytoid DCs in comparison with adult lungs. Yet, when stimulated in vivo by BCG, neonatal lung DCs matured and primed adult naïve CD4(+) T cells toward Th1 as efficiently as adult BCG-primed lung DCs. Conversely, both adult and neonatal BCG-primed lung DCs induced a Th2 cytokine response from neonatal naïve lymph node T cells, suggestive of an intrinsic feature of neonatal T lymphocytes.
authors.affiliation: UR892, INRA, Jouy-en-Josas, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Roux
authors.forename: Aude
authors.initials: A
authors.lastname: Remot
authors.forename: Agnès
authors.initials: A
authors.lastname: Petit-Camurdan
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Nahori
authors.forename: Hélène
authors.initials: H
authors.lastname: Kiefer-Biasizzo
authors.forename: Gilles
authors.initials: G
authors.lastname: Marchal
authors.forename: Micheline
authors.initials: M
authors.lastname: Lagranderie
authors.forename: Sabine
authors.initials: S
authors.lastname: Riffault
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000032:analysis; D039481:CD11b Antigen / Q000032:analysis; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000096:biosynthesis; D039001:Integrin alpha Chains / Q000032:analysis; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis*
chemical_list: D015703:Antigens, CD; D039481:CD11b Antigen; D017252:CD3 Complex; D016207:Cytokines; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D039001:Integrin alpha Chains; D014157:Transcription Factors; C091367:alpha E integrins