AMICA: A New Costimulatory Molecule GammaDelta T Cells

AMICA：一种新的共刺激分子 GammaDelta T 细胞

• 批准号: 7323240
• 负责人: Wendy L. Havran
• 金额: $ 45.13万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7323240
• 关键词: Adhesions; Adult; Affect; Antigen-Presenting Cells; Antigens; Apoptotic; Autoantigens; Binding; CD28 gene; CD8B1 gene; Cell Communication; Cell physiology; Cells; Condition; Data; Disease; Epithelial; Epithelial Cells; Event; Family; Homeostasis; Immune response; In Vitro; Integrins; Intestines; Knock-out; Ligands; Ligation; Localized; Lymphoid; Lymphoid Cell; Mediating; Mitogens; Mus; Numbers; Personal Satisfaction; Play; Population; Production; Rest; Role; Signal Transduction; Site; Skin; Surface; T-Cell Proliferation; T-Cell Receptor; T-Lymphocyte; T-Lymphocyte Subsets; Testing; Tissues; Wound Healing; cytokine; junctional adhesion molecule; keratinocyte; member; novel; programs; prototype; receptor; repaired; research study; response

T cells bearing invariant y5 T cell antigen receptors (TCR) localize to distinct epithelial sites in the adult mouse where they interact with non-classical antigen presenting cells such as epithelial cells. Many of these y8 T cell populations do not express traditional costimulatory molecules such as CD28 suggesting that they may rely on signals delivered through novel receptor-ligand interactions. We have identified AMIGA, a member of the junctional adhesion molecule family, as a costimulatory molecule for epithelial y8 T cells. AMIGA is expressed on all y5 T cells and in vitro mitogen activation leads to upregulated surface expression. Among lymphoid cells, AMIGA is preferentially expressed by y8 T cells although a small subpopulation of CD8+ ap T cells also express AMIGA after activation. Signals delivered through AMIGA costimulate skin and intestinal y5 T cell proliferation and cytokine release but not activation of any ap T cells or lymphoid y5 T cells. We will test the hypothesis that AMIGA expressed by epithelial y8 T cells binds to a ligand expressed on damaged epithelial cells and that interaction between this novel receptor-ligand pair delivers costimulatory signals to the y8T cell that are critical for participation in local immune responses including tissue homeostasis and repair. Together these studies should determine the roles of AMIGA in the activation and function of epithelial y8 T cells and may be applicable for manipulation of y8 T cell responses in epithelial disorders.

携带恒定γ 5 T细胞抗原受体（TCR）的T细胞定位于上皮细胞的不同部位。 成年小鼠，其中它们与非经典抗原呈递细胞如上皮细胞 细胞这些γ 8 T细胞群中的许多不表达传统的共刺激分子 例如CD 28，这表明它们可能依赖于通过新的受体-配体传递的信号， 交互.我们已经鉴定了AMIGA，它是连接粘附分子家族的一员， 作为上皮γ 8 T细胞的共刺激分子。AMIGA在所有γ 5 T细胞上表达， 体外促分裂原活化导致上调的表面表达。在淋巴细胞中， AMIGA优先由γ 8 T细胞表达，尽管CD 8 + ap T细胞的一小部分亚群 细胞在活化后也表达AMIGA。通过AMIGA共刺激皮肤传递的信号 和肠γ 5 T细胞增殖和细胞因子释放，但不激活任何α β T细胞， 淋巴样γ 5 T细胞。我们将检验AMIGA由上皮γ 8 T细胞表达的假设， 与受损上皮细胞上表达的配体结合， 受体-配体对向γ 8 T细胞递送共刺激信号，这对于 参与局部免疫应答，包括组织稳态和修复。综合这些 研究应该确定AMIGA在上皮细胞γ 8 T的激活和功能中的作用， 细胞，并可适用于操纵上皮疾病中的γ 8 T细胞应答。