Friedman Rachel S, Jacobelli Jordan, Krummel Matthew F
The Department of Pathology, University of California at San Francisco, San Francisco, California 94143, USA.
Nat Immunol. 2006 Oct;7(10):1101-8. doi: 10.1038/ni1384. Epub 2006 Sep 10.
T cell activation in vivo occurs in a lymphoid milieu that presents chemotactic and T cell receptor signals concurrently. Here we demonstrate that T cell zone chemokines such as CCL21 are bound to the surface of lymph node dendritic cells. Contact with antigen-presenting cells bearing chemokines costimulated T cells by a previously unknown two-step contact mechanism. T cells initially formed an antigen-independent 'tethered' adhesion on chemokine-bearing antigen-presenting cells. The formation of those tethers superseded T cell receptor signaling and immunological synapse formation. However, chemokine-tethered T cells were hyper-responsive to subsequent contacts with antigen-presenting cells. Thus, T cells are costimulated 'in trans' and sequentially after initial engagement with their chemokine-rich environment.
体内T细胞活化发生在一个同时呈现趋化性和T细胞受体信号的淋巴微环境中。在此,我们证明诸如CCL21等T细胞区趋化因子与淋巴结树突状细胞表面结合。与携带趋化因子的抗原呈递细胞接触通过一种先前未知的两步接触机制共刺激T细胞。T细胞最初在携带趋化因子的抗原呈递细胞上形成抗原非依赖性的“拴系”黏附。这些拴系的形成取代了T细胞受体信号传导和免疫突触形成。然而,趋化因子拴系的T细胞对随后与抗原呈递细胞的接触反应过度。因此,T细胞在最初与其富含趋化因子的环境接触后以“反式”方式并顺序性地受到共刺激。