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The Journal of Immunology, 2001, 166: 3143-3150.
Copyright © 2001 by The American Association of Immunologists

Regulation and Function of T1/ST2 Expression on CD4+ T Cells: Induction of Type 2 Cytokine Production by T1/ST2 Cross-Linking1

Christian Meisel2,3,*, Kerstin Bonhagen2,*, Max Löhning*, Anthony J. Coyle{dagger}, Jose-Carlos Gutierrez-Ramos{dagger}, Andreas Radbruch* and Thomas Kamradt4,*,{ddagger}

* Deutsches Rheumaforschungszentrum, Berlin, Germany; {dagger} Millennium Pharmaceuticals, Cambridge, MA 021139; and {ddagger} Universitätsklinikum Charité, Medizinische Klinik mit Schwerpunkt Rheumatologie/Klinische Immunologie, Berlin, Germany

The orphan receptor T1/ST2, a member of the IL-1R family, is preferentially expressed on the surface of murine Th2 cells. In this study, we analyzed the kinetics and function of T1/ST2 expression on Th2 cells in vitro. Whereas naive CD4+ cells did not express T1/ST2, most CD4+ cells became T1/ST2+ upon repeated antigenic stimulation under Th2-polarizing conditions. Flow cytometric analyses revealed that the kinetics of T1/ST2 expression on Th2 cells was delayed compared with the kinetics of type 2 cytokine production. Exogenous IL-6, IL-5, IL-1, and TNF-{alpha} enhanced the expression of T1/ST2 on Th2 cells, and IL-6 was by far most effective in this regard. However, the expression of T1/ST2 did not depend on the presence of IL-6 and was also detected in IL-6-deficient mice. Most important, cross-linking of T1/ST2 provided a costimulatory signal for Th2 but not Th1 cells and directly induced proliferation and type 2 cytokine production. Thus, T1/ST2 is not only a Th2 cell marker but also plays an important role in the activation of Th2 cells.




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