Antigen-specific effector CD8 T cells regulate allergic responses via IFN-γ and dendritic cell function

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-gamma expressions to modulate the elicitation of allergic inflammation following ovalbumin (OVA) challenge and investigate the underlying mechanisms. Methods: To study the role of IFN-gamma in the effect of CD8 T cells, effector CD8 T cells from CD8 OVA transgenic (OT-I) mice and IFN-gamma(-/-) 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-gamma(-/-) OT-I CD8 T cells, attenuated eosinophilia and mucus secretion in the lungs of sensitized mice in an antigen-specific manner. Effector IFN-gamma(-/-) 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-gamma 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-gamma, CD8 T cells assume a Tc2-/Tc17-biased phenotype and potentiate inflammation. (J Allergy Clin Immunol 2012; 129: 1611-20.)