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

Nat Med. 2004 Aug;10(8):865-9. doi: 10.1038/nm1081. Epub 2004 Jul 18.

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 cells. Previously, two distinct populations of antigen-experienced CD8(+) T cells, termed effector (T(EFF)) and central memory (T(CM)) cells, have been described. After adoptive transfer into CD8-deficient mice, T(EFF), but not T(CM), cells restored AHR, eosinophilic inflammation and IL-13 levels. T(EFF), but not T(CM), cells accumulated in the lungs, and intracellular cytokine staining showed that the transferred T(EFF) 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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adoptive Transfer
  • Allergens / immunology*
  • Alum Compounds
  • Analysis of Variance
  • Animals
  • Bronchial Hyperreactivity / immunology*
  • Bronchial Hyperreactivity / pathology
  • Bronchitis / immunology*
  • Bronchitis / physiopathology
  • Bronchoalveolar Lavage Fluid / immunology
  • CD8 Antigens / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Cytokines / metabolism
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Interleukin-13 / immunology
  • Lung / immunology
  • Lung / pathology
  • Methacholine Chloride
  • Mice
  • Mice, Mutant Strains
  • Ovalbumin
  • T-Lymphocyte Subsets / immunology*

Substances

  • Allergens
  • Alum Compounds
  • CD8 Antigens
  • Cytokines
  • Interleukin-13
  • ovalbumin-alum
  • Methacholine Chloride
  • Ovalbumin