title: Antigen-specific effector CD8 T cells regulate allergic responses via IFN-γ and dendritic cell function.
abstract: BACKGROUND
  Previous studies have shown that CD8 T cells can both prevent and cause allergic responses. However, the underlying mechanisms remain to be elucidated.
  
  
  OBJECTIVE
  We aim to investigate the potential of CD8 T cells with different IFN-γ expressions to modulate the elicitation of allergic inflammation following ovalbumin (OVA) challenge and investigate the underlying mechanisms.
  
  
  METHODS
  To study the role of IFN-γ in the effect of CD8 T cells, effector CD8 T cells from CD8 OVA transgenic (OT-I) mice and IFN-γ(-/-)OT-I mice were transferred to OVA-sensitized mice the day before 3 challenges with OVA. The effect on lung dendritic cells (DCs) exerted by CD8 T cells was studied with ex vivo culture of sorted DCs from treatment mice with CD4 T cells.
  
  
  RESULTS
  Effector OT-I, but not IFN-γ(-/-)OT-I CD8 T cells, attenuated eosinophilia and mucus secretion in the lungs of sensitized mice in an antigen-specific manner. Effector IFN-γ(-/-)OT-I CD8 T cells displayed a Tc2-/Tc17-biased phenotype with weaker cytotoxicity and were able to both induce and exacerbate eosinophilia as well as neutrophilia. OT-I CD8 T cells increased the ability of lung CD11b(+)CD103(-) DCs to both prime the differentiation of naive OVA-specific CD4 T cells toward a T(H)1 phenotype and enhance IFN-γ production by antigen-experienced lung CD4 T cells.
  
  
  CONCLUSIONS
  Effector CD8 T cells attenuate pulmonary inflammation and alter the ability of DCs within the allergic lung to polarize T cells to a T(H)1 phenotype during a T(H)2 response. In the absence of IFN-γ, CD8 T cells assume a Tc2-/Tc17-biased phenotype and potentiate inflammation.
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Yafang
authors.initials: Y
authors.lastname: Tang
authors.forename: Shou Ping
authors.initials: SP
authors.lastname: Guan
authors.forename: Benson Y L
authors.initials: BY
authors.lastname: Chua
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhou
authors.forename: Adrian W S
authors.initials: AW
authors.lastname: Ho
authors.forename: Kenneth H S
authors.initials: KH
authors.lastname: Wong
authors.forename: Kok Loon
authors.initials: KL
authors.lastname: Wong
authors.forename: W S Fred
authors.initials: WS
authors.lastname: Wong
authors.forename: David M
authors.initials: DM
authors.lastname: Kemeny
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D020397:Goblet Cells / Q000378:metabolism; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009093:Mucus; D010641:Phenotype; D018417:Th1 Cells / Q000166:cytology
chemical_list: D007371:Interferon-gamma