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CD8⁺ T Cell-Mediated Airway Hyperresponsiveness and Inflammation Is Dependent on CD4⁺IL-4⁺ T Cells¹

Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206

CD4⁺ T cells, particularly Th2 cells, play a pivotal role in allergic airway inflammation. However, the requirements for interactions between CD4⁺ and CD8⁺ T cells in airway allergic inflammation have not been delineated. Sensitized and challenged OT-1 mice in which CD8⁺ T cells expressing the transgene for the OVA_257–264 peptide (SIINFEKL) failed to develop airway hyperresponsiveness (AHR), airway eosinophilia, Th2 cytokine elevation, or goblet cell metaplasia. OT-1 mice that received naive CD4⁺IL-4⁺ T cells but not CD4⁺IL-4^– T cells before sensitization developed all of these responses to the same degree as wild-type mice. Moreover, recipients of CD4⁺IL-4⁺ T cells developed significant increases in the number of CD8⁺IL-13⁺ T cells in the lung, whereas sensitized OT-1 mice that received primed CD4⁺ T cells just before challenge failed to develop these responses. Sensitized CD8-deficient mice that received CD8⁺ T cells from OT-1 mice that received naive CD4⁺ T cells before sensitization increased AHR and eosinophil numbers in bronchoalveolar lavage fluid when challenged with allergen. In contrast, sensitized CD8-deficient mice receiving CD8⁺ T cells from OT-1 mice without CD4⁺ T cells developed reduced AHR and eosinophil numbers in bronchoalveolar lavage fluid when challenged. These data suggest that interactions between CD4⁺ and CD8⁺ T cells, in part through IL-4 during the sensitization phase, are essential to the development of CD8⁺IL-13⁺ T cell-dependent AHR and airway allergic inflammation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Grants HL-36577 and HL-61005 from the National Institutes of Health and Grant R825702 from the Environmental Protection Agency.

² Address correspondence and reprint requests to Dr. Erwin W. Gelfand, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206. E-mail address: gelfande{at}njc.org

³ Abbreviations used in this paper: AHR, airway hyperresponsiveness; BAL, bronchoalveolar lavage; MNC, mononuclear cell; PAS, Periodic acid-Schiff; WT, wild type.

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