J. Exp. Med., Volume 187, Number 5, March 2, 1998 787-794

Selective Expression of a Stable Cell Surface Molecule on Type 2 but Not Type 1 Helper T Cells

By Damo Xu,^* Woon Ling Chan, Bernard P. Leung,^* Fang-ping Huang,^* Rachel Wheeler, David Piedrafita,^* John H. Robinson,^§ and Foo Y. Liew^*

From the ^* Department of Immunology, University of Glasgow, Glasgow G11 6NT, United Kingdom; the  Department of Virology, St. Bartholomew and Royal London School of Medicine, QMW College, University of London, London EC1A 7BE, United Kingdom; and the ^§ Department of Immunology, University of Newcastle, Newcastle Upon Tyne NE2 4HH, United Kingdom

T helper cell type 1 (Th1) and 2 (Th2) are central to immune regulation. However, no stable cell surface marker capable of distinguishing and separating these two subsets of CD4⁺ cells has yet been found. Using differential display PCR, we have identified a gene encoding a cell membrane bound molecule, originally designated ST2L, T1, DER4, or Fit, expressed constitutively and stably on the surface of murine Th2s, but not Th1s even after stimulation with a range of immunological stimuli. Antibody against a peptide derived from ST2L strongly and stably labeled the surface of cloned Th2s but not Th1s, and Th2s but not Th1s derived from naive T cells of ovalbumin T cell receptor-/ transgenic mice. Three-color single cell flow cytometric analysis shows that cell surface ST2L coexpressed with intracellular interleukin (IL)-4, but not with interferon (IFN)-. The antibody selectively lysed Th2s in vitro in a complement-dependent manner. In vivo, it enhanced Th1 responses by increasing IFN- production and decreasing IL-4 and IL-5 synthesis. It induced resistance to Leishmania major infection in BALB/c mice and exacerbated collagen-induced arthritis in DBA/1 mice. Thus, ST2L is a stable marker distinguishing Th2s from Th1s and is also associated with Th2 functions. Hence, it may be a target for therapeutic intervention.

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