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. CONCLUSION: 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.
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. CONCLUSION: 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: C B Mathias; C M Schramm; L A Guernsey; C A Wu; S H Polukort; J Rovatti; J Ser-Dolansky; E Secor; S S Schneider; R S Thrall; H L Aguila Journal: Clin Exp Allergy Date: 2017-02-07 Impact factor: 5.018
Authors: N J Daniels; E Hyde; S Ghosh; K Seo; K M Price; K Hoshino; T Kaisho; T Okada; F Ronchese Journal: Mucosal Immunol Date: 2015-06-24 Impact factor: 7.313
Authors: Yi Jia; Joanne Domenico; Katsuyuki Takeda; Junyan Han; Meiqin Wang; Michael Armstrong; Nichole Reisdorph; Brian P O'Connor; Joseph J Lucas; Erwin W Gelfand Journal: Proc Natl Acad Sci U S A Date: 2013-04-29 Impact factor: 11.205
Authors: Yen Leong Chua; Ka Hang Liong; Chiung-Hui Huang; Hok Sum Wong; Qian Zhou; Say Siong Ler; Yafang Tang; Chin Pei Low; Hui Yu Koh; I-Chun Kuo; Yongliang Zhang; W S Fred Wong; Hong Yong Peh; Hwee Ying Lim; Moyar Qing Ge; Angela Haczku; Veronique Angeli; Paul A MacAry; Kaw Yan Chua; David M Kemeny Journal: J Immunol Date: 2016-10-12 Impact factor: 5.422