SELECTIVE EXPRESSION OF A STABLE CELL-SURFACE MOLECULE ON TYPE-2 BUT NOT TYPE-1 HELPER T-CELLS

T helper cell type 1 (Th1) and 2 (Th2) are central to immune regulatio n. However, no stable cell surface marker capable of distinguishing an d separating these two subsets of CD4(+) cells has yet been found. Usi ng 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 This even after stimulation with a range of immunological stim uli. Antibody against a peptide derived from ST2L strongly and stably labeled the surface of cloned Th2s but not This, and Th2s but not This derived from naive T cells of ovalbumin T cell receptor-alpha/beta tr ansgenic mice. Three-color single cell now cytometric analysis shows t hat cell surface ST2L coexpressed with intracellular interleukin (IL)- 4, but not with interferon (IFN)-gamma. The antibody selectively lysed Th2s in vitro in a complement-dependent manner. In vivo, it enhanced Th1 responses by increasing IFN-gamma production and decreasing IL-4 a nd IL-5 synthesis. It induced resistance to Leishmania major infection in BALB/c mice and exacerbated collagen-induced arthritis in DBA/1 mi ce. Thus, ST2L is a stable marker distinguishing Th2s from This and is also associated with Th2 functions. Hence, it may be a target for the rapeutic intervention.