T1/ST2 is preferentially expressed on murine Th2 cells, independent of interleukin 4, interleukin 5, and interleukin 10, and important for Th2 effector function

T1/ST2 is preferentially expressed on murine Th2 cells, independent of interleukin 4, interleukin 5, and interleukin 10, and important for Th2 effector function

^*Deutsches Rheumaforschungszentrum, 10117 Berlin, Germany; ^‡Universitätsklinik Charité, III. Medizinische Klinik, 10098 Berlin, Germany; and ^§Millennium Pharmaceuticals, Cambridge, MA 02139

Communicated by N. Avrion Mitchison, National Institutes of Health, Bethesda, MD (received for review February 10, 1998)

Abstract

T helper (Th) cells can be categorized according to their cytokine expression. The differential induction of Th cells expressing Th1 and/or Th2 cytokines is key to the regulation of both protective and pathological immune responses. Cytokines are expressed transiently and there is a lack of stably expressed surface molecules, significant for functionally different types of Th cells. Such molecules are of utmost importance for the analysis and selective functional modulation of Th subsets and will provide new therapeutic strategies for the treatment of allergic or autoimmune diseases. To this end, we have identified potential target genes preferentially expressed in Th2 cells, expressing interleukin (IL)-4, IL-5, and/or IL-10, but not interferon-γ. One such gene, T1/ST2, is expressed stably on both Th2 clones and Th2-polarized cells activated in vivo or in vitro. T1/ST2 expression is independent of induction by IL-4, IL-5, or IL-10. T1/ST2 plays a critical role in Th2 effector function. Administration of either a mAb against T1/ST2 or recombinant T1/ST2 fusion protein attenuates eosinophilic inflammation of the airways and suppresses IL-4 and IL-5 production in vivo following adoptive transfer of Th2 cells.

Footnotes

↵ † M.L. and A.S. contributed equally to this work.
↵ ¶ To whom requests for antibodies should be addressed. e-mail: Levinson{at}mpi.com.
↵ ‖ To whom reprint requests should be addressed at: Deutsches Rheumaforschungszentrum, Monbijoustrasse 2, 10117 Berlin, Germany. e-mail: Kamradt{at}drfz.de.
ABBREVIATIONS:

Th,

T helper;

IL,

interleukin;

IFN,

interferon;

TNF,

tumor necrosis factor;

BAL,

bronchoalveolar lavage;

TCR,

T-cell antigen receptor;

FITC,

fluorescein isothiocyanate;

PE,

phycoerythrin;

DIG,

digoxigenin;

wt,

wild type;

PMA,

phorbol 12-myristate 13-acetate;

MACS,

magnetic cell separation system