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

• Published in: The Journal of immunology (1950) Vol. 179; no. 5; pp. 2787 - 2796
• Main Authors: Koya, Toshiyuki, Miyahara, Nobuaki, Takeda, Katsuyuki, Matsubara, Shigeki, Matsuda, Hiroyuki, Swasey, Christina, Balhorn, Annette, Dakhama, Azzeddine, Gelfand, Erwin W
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.09.2007
• Subjects: Adoptive Transfer; Animals; Asthma - immunology; Asthma - prevention & control; Bronchial Hyperreactivity - immunology; Bronchial Hyperreactivity - prevention & control; CD4 Antigens - analysis; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Egg Proteins - genetics; Egg Proteins - metabolism; Inflammation - immunology; Inflammation - prevention & control; Interleukin-4 - administration & dosage; Interleukin-4 - genetics; Interleukin-4 - metabolism; Mice; Mice, Transgenic; Ovalbumin - genetics; Ovalbumin - metabolism; Peptide Fragments; Transgenes
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.179.5.2787

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.