Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.148 (Thy1)
 1,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Costimulatory activity on antigen-presenting cells is a critical determinant of the fate T cells when the T cell receptors are engaged by MHC:peptide complexes. Therefore, control of the expression of the costimulatory molecules regulates T cell responses. While several types of interactions between T cells and B cells up-regulate costimulatory molecules on antigen-presenting cell, no T cell surface molecules have been implicated in inhibiting the induction of the costimulatory molecules on B cells. Here we characterize a new anti-Thy1 mAb, 21F10, which inhibits T cell proliferation to selective stimuli. T cells stimulated by anti-CD3 together with anti-Thy1 mAb are anergic to further stimulation through the CD3, which suggests that the anti-Thy1 mAb interferes with the delivery of the costimulatory activity to T cells. Consistent with this notion, anti-Thy1 mAb 21F10 completely inhibits the induction of B7-2 on B cells. Induction of several T cell surface molecules such as CD69 and CD40 ligand was largely unaffected. As this inhibition requires a bivalent anti-Thy1 mAb and does not require binding of more than 50% of Thy1 molecules on T cell surface, we suggest that Thy1 may mediate a negative signaling pathway which inhibits the T-cell-mediated induction of costimulatory activity, including expression of co-stimulatory molecule B7-2.
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PMID:Signaling by a new anti-Thy 1 monoclonal antibody inhibits T cell proliferation and interferes with T-cell-mediated induction of costimulatory molecule B7-2. 755 91

The recruitment of eosinophils into the airways after allergen exposure is dependent on interleukin (IL) 5 secreted from antigen-specific CD4+ T cells of the T helper cell (Th) 2 subset. However, while it is established that costimulation through CD28 is required for TCR-mediated activation and IL-2 production, the importance of this mechanism for the induction of a Th2 immune response is less clear. In the present study, we administered the fusion protein CTLA-4 immunoglobulin (Ig) into the lungs before allergen provocation to determine whether CD28/CTLA-4 ligands are required for allergen-induced eosinophil accumulation and the production of Th2 cytokines. Administration of CTLA-4 Ig inhibited the recruitment of eosinophils into the lungs by 75% and suppressed IgE in the bronchoalveolar lavage fluid. CTLA-4 Ig also inhibited the production of IL-4, IL-5, and IL-10 by 70-80% and enhanced interferon-gamma production from CD3-T cell receptor-activated lung Thy1.2+ cells. Allergen exposure upregulated expression of B7-2, but not B7-1, on B cells from the lung within 24 h. Moreover, airway administration of an anti-B7-2 monoclonal antibody (mAb) inhibited eosinophil infiltration, IgE production, and Th2 cytokine secretion comparable in magnitude to that observed with CTLA-4 Ig. Treatment with an anti-B7-1 mAb had a small, but significant effect on eosinophil accumulation, although was less effective in inhibiting Th2 cytokine production. The anti-B7-2, but not anti-B7-1, mAb also inhibited antigen-induced airway hyperresponsiveness in vivo. In all of the parameters assessed, the combination of both the anti-B7-1 and anti-B7-2 mAb was no more effective than anti-B7-2 mAb treatment alone. We propose that strategies aimed at inhibition of CD28 interactions with B7-2 molecules may represent a novel therapeutic target for the treatment of lung mucosal allergic inflammation.
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PMID:Costimulation through B7-2 (CD86) is required for the induction of a lung mucosal T helper cell 2 (TH2) immune response and altered airway responsiveness. 915 4