Identification of Th cells in vivo and analysis of differentiation and function of Th2 cells by costimulatory molecules

1.ICOS是共刺激分子CD28家族的新成员，表达于活化的T细胞上。其配体B7RP-1在B细胞上结构性表达。尽管ICOS/B7RP-1相互作用的阻断抑制了T细胞依赖的抗体的产生和生发中心的形成，但其机制尚不清楚。我们推测ICOS/B7RP-1的相互作用可能需要上调CD4T细胞上趋化因子受体CXCR5的表达。CXCR5对B淋巴细胞趋化因子(CXCL13)具有反应性。CD4^+T细胞的一个亚群也表达CXCR5，CXCR5介导它们迁移到B细胞滤泡，在那里它们为B细胞提供同源帮助。因此，CXCR5^+CD4^+T细胞被称为滤泡辅助性T(Th)细胞。以往的研究表明，作为一对TNFR/TNF家族成员，OX40/OX40配体(OX40L)相互作用参与了CXCR5在CD4^+T细胞上的表达。因此，我们比较了ICOS/B7RP-1和OX40/OX40L对CXC…发展的贡献R5~+、CD~4~+滤泡Th细胞和GC B细胞较多。我们的结果表明，ICOS/B7RP-1的相互作用对滤泡性Th细胞在脾和淋巴结中的形成起重要作用，但淋巴结内GC的形成并不总是依赖滤泡性Th细胞。另一方面，OX40/OX40L相互作用对滤泡性Th细胞和GC B细胞的发育只在某些品系的小鼠的淋巴结中有显著贡献，这取决于滤泡性Th细胞上OX40的差异表达。我们还在脾和LN中发现了活化的CD4^+T细胞亚群(CXCR5^+ICOS^+OX40^-细胞、CXCR5^-ICOS^+OX40^-细胞、CXCR5^-ICOS^-OX40^+细胞和CXCR5^-ICOS^+OX40^+细胞)。这三个CXCR5^-群体可能代表在活体中产生Th1或Th2细胞因子的功能不同的亚群。我们证明IOCs在NKT细胞激活中作为共刺激分子发挥作用，从而增加细胞因子的产生和细胞毒活性。较少

1. ICOS is a new member of the CD28 family of costimulatory molecules that is expressed on activated T cells. Its ligand B7RP-1 is constitutively expressed on B cells. Although the blockade of ICOS/B7RP-1 interaction inhibits T cell-dependent Ab production and germinal center formation, the mechanism remains unclear. We speculated that the ICOS/B7RP-1 interaction might be required to up-regulate the expression of a chemokine receptor CXCR5 on CD4 T cells. CXCR5 confers responsiveness to B lymphocyte chemokine (CXCL13). A subset of CD4^+ T cells also express CXCR5, which mediates their migration to the B cell follicles where they provide cognate help to B cells. Thus, CXCR5^+ CD4^+ T cells are referred to as follicular helper T (Th) cells. Previous studies have implicated OX40/OX40 ligand (OX40L) interaction, a pair of the TNFR/TNF family members, in the expression of CXCR5 on CD4^+ T cells. Therefore, we compared the contributions of ICOS/B7RP-1 and OX40/OX40L to the development of CXC … More R5^+ CD4^+ follicular Th cells and GC B cells. Our results indicated that the ICOS/B7RP-1 interaction plays an essential role of follicular Th cells in the spleen and lymph nodes, but the GC formation in lymph nodes is not always dependent on follicular Th cells. On the other hand, a substantial contribution of OX40/OX40L interaction to the development of follicular Th cells and GC B cells was observed only in lymph nodes of certain strains of mice, depending on differential expression of OX40 on follicular Th cells. We also found sub-populations of activated CD4^+ T cells (CXCR5^+ ICOS^+ OX40^- cells, CXCR5^- ICOS^+ OX40^- cells, CXCR5^- ICOS^- OX40^+ cells, and CXCR5^- ICOS^+ OX40^+ cells) in the spleen and LN. It is possible that the three CXCR5^- populations may represent functionally distinct subsets producing Th1 or Th2 cytokines in vivo.2. We demonstrated that IOCS play a role as costimulatory molecules in NKT cell activation, which augments cytokines production and cytotoxic activity. Less