The Journal of Experimental Medicine
Avanti Polar Lipids
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Published online 13 January 2003 doi:10.1084/jem.20020632
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© Rockefeller University Press, 0022-1007/2003/1/181 $5.00
The Journal of Experimental Medicine, Volume 197, Number 2, 181-193

Expression of ICOS In Vivo Defines CD4+ Effector T Cells with High Inflammatory Potential and a Strong Bias for Secretion of Interleukin 10

Max Löhning1, Andreas Hutloff2, Tilmann Kallinich2,3, Hans Werner Mages2, Kerstin Bonhagen1, Andreas Radbruch1, Eckard Hamelmann3 and Richard A. Kroczek2

1 Deutsches Rheumaforschungszentrum, Schumannstrasse 21/22, D-10117 Berlin, Germany
2 Molecular Immunology, Robert Koch-Institute, Nordufer 20, D-13353 Berlin, Germany
3 Pediatric Pneumology and Immunology, Charité, Humboldt University, Augustenburger Platz 1, D-13353 Berlin, Germany

Address correspondence to Richard A. Kroczek, Molecular Immunology, Robert Koch-Institute, Nordufer 20, D-13353 Berlin, Germany. Phone: 49-1888-754-2450; Fax: 49-1888-754-2603; E-mail: kroczek{at}rki.de

The studies performed to date analyzed the overall participation of the inducible costimulator (ICOS) in model diseases, but did not yield information on the nature and function of ICOS-expressing T cells in vivo. We examined ICOS+ T cells in the secondary lymphoid organs of nonmanipulated mice, in the context of an "unbiased" immune system shaped by environmental antigens. Using single cell analysis, ICOSlow cells were found to be loosely associated with the early cytokines interleukin (IL)-2, IL-3, IL-6, and interferon (IFN)-{gamma}. ICOSmedium cells, the large majority of ICOS+ T cells in vivo, were very tightly associated with the synthesis of the T helper type 2 (Th2) cytokines IL-4, IL-5, and IL-13, and these cells exhibited potent inflammatory effects in vivo. In contrast, ICOShigh T cells were highly and selectively linked to the anti-inflammatory cytokine IL-10. Overall, these data seem to indicate that ICOS cell surface density serves as a regulatory mechanism for the release of cytokines with different immunological properties. Further in vivo functional experiments with in vitro–activated T cells strongly suggested that the ICOS+ population, although representing in vivo only around 10% of T cells bearing early or late activation markers, nevertheless encompasses virtually all effector T cells, a finding with major diagnostic and therapeutic implications.

Key Words: T helper cell • T lymphocyte subsets • Th2 cells • cytokine • inflammation


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