The Journal of Experimental Medicine
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Published online 5 March 2001.
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© The Rockefeller University Press, 0022-1007/2001/3/573/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 5, March 5, 2001 573-584


Original Article

Aberrant in Vivo T Helper Type 2 Cell Response and Impaired Eosinophil Recruitment in Cc Chemokine Receptor 8 Knockout Mice

Stephen W. Chensuea, Nicholas W. Lukacsa, Tong-Yuan Yangf, Xiaozhou Shanga, Kirsten A. Fraita, Steven L. Kunkela, Ted Kungf, Maria T. Wiekowskif, Joseph A. Hedrickd, Donald N. Cookf, Alessandra Zingonib, Satwant K. Narulaf, Albert Zlotnike, Franck J. Barrate, Anne O'Garrae, Monica Napolitanoc, and Sergio A. Liraf

a Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48105
b Department of Experimental Medicine and Pathology, University of Rome, 00167 Rome, Italy
c Instituto Dermopatico dell'Immacolata-IRCCS, 00167 Rome, Italy
d Human Genome Research, Palo Alto, California 94304
e DNAX Research Institute for Cellular and Molecular Biology, Palo Alto, California 94304
f Department of Immunology, Schering-Plough Research Institute, Kenilworth, New Jersey 07033
Department of Immunology K15 D-210C, Schering-Plough Research Institute, 2015 Galloping Hill Rd., Kenilworth, NJ 07033-0539.908-740-3084908-740-3088

sergio.lira{at}spcorp.com

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.

Key Words: chemokine receptors • chemokines • T helper type 2 cells • allergy • granulomas


Abbreviations used in this paper: ANOVA, analysis of variance; BAL, bronchoalveolar lavage; CCR, CC chemokine receptor; CRA, cockroach antigen; CXCR, CXC chemokine receptor; EPO, eosinophil peroxidase; ES, embryonic stem; FBS, fetal bovine serum; PPD, purified protein derivative; RT, reverse transcription; SEA, schistosome egg antigen; TCA, T cell activation–specific gene 3.

© 2001 The Rockefeller University Press


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