Aberrant in vivo T helper type 2 cell response and impaired eosinophil recruitment in CC chemokine receptor 8 knockout mice

Stephen W. Chensue, Nicholas W. Lukacs, Tong Yuan Yang, Xiaozhou Shang, Kirsten A. Frait, Steven L. Kunkel, Ted Kung, Maria T. Wiekowski, Joseph A. Hedrick, Donald N. Cook, Alessandra Zingoni, Satwant K. Narula, Albert Zlotnik, Franck J. Barrat, Anne O'Garra, Monica Napolitano, Sergio A. Lira

Research output: Contribution to journalArticle

Abstract

Chemokine receptors transduce signals important for the function and trafficking of leukocytes. Recently, it has been shown that CC chemokine receptor (CCR)8 is selectively expressed by Th2 subsets, but its functional relevance is unclear. To address the biological role of CCR8, we generated CCR8 deficient (-/-) mice. Here we report defective T helper type 2 (Th2) immune responses in vivo in CCR8-/- mice in models of Schistosoma mansoni soluble egg antigen (SEA)-induced granuloma formation as well as ovalbumin (OVA)- and cockroach antigen (CRA)-induced allergic airway inflammation. In these mice, the response to SEA, OVA, and CRA showed impaired Th2 cytokine production that was associated with aberrant type 2 inflammation displaying a 50 to 80% reduction in eosinophils. In contrast, a prototypical Th1 immune response, elicited by Mycobacteria bovis purified protein derivative (PPD) was unaffected by CCR8 deficiency. Mechanistic analyses indicated that Th2 cells developed normally and that the reduction in eosinophil recruitment was likely due to systemic reduction in interleukin 5. These results indicate an important role for CCR8 in Th2 functional responses in vivo.

Original languageEnglish
Pages (from-to)573-584
Number of pages12
JournalJournal of Experimental Medicine
Volume193
Issue number5
DOIs
Publication statusPublished - Mar 5 2001

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Keywords

  • Allergy
  • Chemokine receptors
  • Chemokines
  • Granulomas
  • T helper type 2 cells

ASJC Scopus subject areas

  • Immunology

Cite this

Chensue, S. W., Lukacs, N. W., Yang, T. Y., Shang, X., Frait, K. A., Kunkel, S. L., Kung, T., Wiekowski, M. T., Hedrick, J. A., Cook, D. N., Zingoni, A., Narula, S. K., Zlotnik, A., Barrat, F. J., O'Garra, A., Napolitano, M., & Lira, S. A. (2001). Aberrant in vivo T helper type 2 cell response and impaired eosinophil recruitment in CC chemokine receptor 8 knockout mice. Journal of Experimental Medicine, 193(5), 573-584. https://doi.org/10.1084/jem.193.5.573