Leukotriene B4 receptor-1 is essential for allergen-mediated recruitment of CD8+ T cells and airway hyperresponsiveness

J Immunol. 2005 Apr 15;174(8):4979-84. doi: 10.4049/jimmunol.174.8.4979.

Abstract

Recent studies in both human and rodents have indicated that in addition to CD4+ T cells, CD8+ T cells play an important role in allergic inflammation. We previously demonstrated that allergen-sensitized and -challenged CD8-deficient (CD8-/-) mice develop significantly lower airway hyperresponsiveness (AHR), eosinophilic inflammation, and IL-13 levels in bronchoalveolar lavage fluid compared with wild-type mice, and that all these responses were restored by adoptive transfer of in vivo-primed CD8+ T cells or in vitro-generated effector CD8+ T cells (T(EFF)). Recently, leukotriene B4 and its high affinity receptor, BLT1, have been shown to mediate in vitro-generated T(EFF) recruitment into inflamed tissues. In this study we investigated whether BLT1 is essential for the development of CD8+ T cell-mediated allergic AHR and inflammation. Adoptive transfer of in vivo-primed BLT1+/+, but not BLT1-/-, CD8+ T cells into sensitized and challenged CD8-/- mice restored AHR, eosinophilic inflammation, and IL-13 levels. Moreover, when adoptively transferred into sensitized CD8-/- mice, in vitro-generated BLT1+/+, but not BLT1-/-, T(EFF) accumulated in the lung and mediated these altered airway responses to allergen challenge. These data are the first to show both a functional and an essential role for BLT1 in allergen-mediated CD8+ T(EFF) recruitment into the lung and development of AHR and airway inflammation.

Publication types

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

MeSH terms

  • Adoptive Transfer
  • Allergens / administration & dosage*
  • Animals
  • Bronchial Hyperreactivity / immunology*
  • Bronchoalveolar Lavage Fluid / immunology
  • CD8 Antigens / genetics
  • CD8 Antigens / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Movement
  • Cytokines / metabolism
  • Egg Proteins / administration & dosage
  • Egg Proteins / immunology
  • Eosinophils / immunology
  • Female
  • Humans
  • In Vitro Techniques
  • Lung / cytology
  • Lung / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Peptide Fragments
  • Receptors, Leukotriene B4 / metabolism*

Substances

  • Allergens
  • CD8 Antigens
  • Cytokines
  • Egg Proteins
  • OVA-8
  • Peptide Fragments
  • Receptors, Leukotriene B4
  • Ovalbumin