CD8+ T cell-mediated airway hyperresponsiveness and inflammation is dependent on CD4+IL-4+ T cells.
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.
Koya
Toshiyuki
T
Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Miyahara
Nobuaki
N
Takeda
Katsuyuki
K
Matsubara
Shigeki
S
Matsuda
Hiroyuki
H
Swasey
Christina
C
Balhorn
Annette
A
Dakhama
Azzeddine
A
Gelfand
Erwin W
EW
D019264:Adoptive Transfer; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000517:prevention & control; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000517:prevention & control; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004527:Egg Proteins / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D015847:Interleukin-4 / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments; D019076:Transgenes
D015704:CD4 Antigens; D004527:Egg Proteins; C110366:OVA-8; D010446:Peptide Fragments; D015847:Interleukin-4; D010047:Ovalbumin