Effector CD8+ T cells mediate inflammation and airway hyper-responsiveness

Abstract

Allergic asthma is a complex syndrome characterized by airway obstruction, airway inflammation and airway hyper-responsiveness (AHR). Using a mouse model of allergen-induced AHR, we previously demonstrated that CD8-deficient mice develop significantly lower AHR, eosinophilic inflammation and interleukin (IL)-13 levels in bronchoalveolar lavage fluid compared with wild-type mice. These responses were restored by adoptive transfer of antigen-primed CD8+ T cells1. Previously, two distinct populations of antigen-experienced CD8+ T cells, termed effector (TEFF) and central memory (TCM) cells, have been described2,3,4,5. After adoptive transfer into CD8-deficient mice, TEFF, but not TCM, cells restored AHR, eosinophilic inflammation and IL-13 levels. TEFF, but not TCM, cells accumulated in the lungs, and intracellular cytokine staining showed that the transferred TEFF cells were a source of IL-13. These data suggest an important role for effector CD8+ T cells in the development of AHR and airway inflammation, which may be associated with their Tc2-type cytokine production and their capacity to migrate into the lung.

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Figure 1: Reconstitution of lung allergic responses with TEFF and not TCM.
Figure 2: Cytokine levels are restored following transfer of TEFF but not TCM.

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Acknowledgements

We thank J. Cambier, P. Marrack and J. Kappler for support; J.J. Lee for the antibody to major basic protein; and L.N. Cunningham and D. Nabighian for assistance. This work was supported by National Institute of Health grants HL-36577, HL-61005 and AI-42246 and Environmental Protection Agency grants R825702 (E.W.G.) and AI-52225.

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Correspondence to Erwin W Gelfand.

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Supplementary information

Supplementary Fig. 1

Preferential treatment of TEFF in the lung (PDF 153 kb)

Supplementary Fig. 2

Quantitation of TEFF or TCM in the lung sections from the submucosal tissue around the major airways or peripheral tissue. (PDF 20 kb)

Supplementary Fig. 3

Histograms of CFSE-labeled TEFF and TCM prior to transfer and following recovery from the lungs and PBLN, respectively, of sensitized and challenged CD8-deficient mice. (PDF 23 kb)

Supplementary Fig. 4

Intracellular staining for IL-4, IL-5, IL-13, and IFN-γ in CD8+ T cells from OVA sensitized and challenged recipient CD8-deficient mice following transfer of TCM. (PDF 22 kb)

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Miyahara, N., Swanson, B., Takeda, K. et al. Effector CD8+ T cells mediate inflammation and airway hyper-responsiveness. Nat Med 10, 865–869 (2004). https://doi.org/10.1038/nm1081

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