Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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-alpha/beta 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)-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 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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PMID:Selective expression of a stable cell surface molecule on type 2 but not type 1 helper T cells. 948 Sep 88

Expression of the T1 gene, also known as ST2, DER4, and Fit-1, has been shown to be associated with cell proliferation. It gives rise to two different mRNAs that encode a receptor-like protein and a soluble molecule representing the ectodomain of the receptor form. Although T1 is a member of the IL-1R family, its biologic function is currently unknown. In this study, we have analyzed the expression of the T1 surface Ag in murine hemopoietic organs. Mast cells (MCs) were shown to be the only identifiable cell lineage that expressed T1 at high levels. T1 expression was found on cultured bone marrow-derived immature MCs. Similarly, freshly isolated connective tissue-type MCs from the i.p. cavity were also shown to express high levels of T1. Interestingly, the earliest detectable committed MC precursor isolated from fetal blood (FB) at day 15.5 of gestation, but not circulating hemopoietic stem cells in FB, also expresses high level of T1. Since FB promastocytes lack expression of the high affinity IgE receptor (Fc epsilonRI), T1 expression precedes expression of Fc epsilonRI in MC ontogeny. The finding that the T1 Ag is selectively expressed at several stages during development of the MC lineage suggests that this cell surface molecule, in combination with the well-established markers c-Kit and Fc epsilonRI, should be valuable for studying the MC lineage.
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PMID:The IL-1 receptor-related T1 antigen is expressed on immature and mature mast cells and on fetal blood mast cell progenitors. 979 20

Th2-associated factors such as IL-4 are involved in both the development of Th2 responses (via modulating Th2 cell differentiation) and in the effector phase of Th2 responses (via modulating macrophage activation). The IL-1 receptor-like protein ST2 (T1, Fit-1, or DER4) is expressed as a membrane-bound (ST2L) or secreted form (sST2), and has been clearly implicated as a regulator of both the development and effector phases of Th2-type responses. Here we analyze the mechanisms and therapeutic implications of the unique ability of ST2 to promote development and function of type 2 helper T cells through a positive feedback loop, as well as to act as a negative feedback modulator of macrophage pro-inflammatory function.
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PMID:T1/ST2--an IL-1 receptor-like modulator of immune responses. 1511 Jul 92