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

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• 作者：Yafang Tang ; BSc^a ; ^b ; ^c ; Shou Ping Guan ; BSc^b ; ^d ; Benson Y.L. Chua ; BSc^a ; ^b ; Qian Zhou ; BSc^a ; ^b ; Adrian W.S. Ho ; BSc^a ; ^b ; Kenneth H.S. Wong ; BSc^a ; ^b ; Kok Loon Wong ; PhD^e ; W.S. Fred Wong ; PhD^b ; ^d ; David M. Kemeny ; PhD ; FRCPath^a ; ^b ; ^c ; ^{mickdm@nus.edu.sg}
• 关键词：Asthma ; OT-I ; IFN-纬&minus ; /&minus ; OT-I ; CD8 T cells ; effector ; IFN-纬 ; eosinophils ; CD11b+CD103&minus ; DC ; TH1
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2012
• 期刊代码：158_00916749
• 类别：med
• 出版时间：June, 2012
• 卷：129
• 期：6
• 页码：1611-1620.e4
• 文件大小：1709 K

摘要

| Figures/TablesFigures/Tables | ReferencesReferences<h4 class="h4">Backgroundh4>Previous studies have shown that CD8 T cells can both prevent and cause allergic responses. However, the underlying mechanisms remain to be elucidated.<h4 class="h4">Objectiveh4>

We aim to investigate the potential of CD8 T cells with different IFN-纬 expressions to modulate the elicitation of allergic inflammation following ovalbumin (OVA) challenge and investigate the underlying mechanisms.<h4 class="h4">Methodsh4>

To study the role of IFN-纬 in the effect of CD8 T cells, effector CD8 T cells from CD8 OVA transgenic (OT-I) mice and IFN-纬^{鈭?鈭?/sup>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聽vivo culture of sorted DCs from treatment mice with CD4 T cells.<h4 class="h4">Resultsh4>}

Effector OT-I, but not IFN-纬^{鈭?鈭?/sup>OT-I CD8 T cells, attenuated eosinophilia and mucus secretion in the lungs of sensitized mice in an antigen-specific manner. Effector IFN-纬鈭?鈭?/sup>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鈭?/sup> DCs to both prime the differentiation of naive OVA-specific CD4 T cells toward a T_H1 phenotype and enhance IFN-纬 production by antigen-experienced lung CD4 T cells.<h4 class="h4">Conclusionh4>}

Effector CD8 T cells attenuate pulmonary inflammation and alter the ability of DCs within the allergic lung to polarize T cells to a T_H1 phenotype during a T_H2 response. In the absence of IFN-纬, CD8 T cells assume a Tc2-/Tc17-biased phenotype and potentiate inflammation.