Chemokines and T lymphocyte activation: I. Beta chemokines costimulate human T lymphocyte activation in vitro

作者：Dennis Daniel Taub, Susan M. Turcovski‐Corrales, M L Key, Dan L. Longo, William J. Murphy · 发表于：The Journal of Immunology · 年份：1996 · DOI：10.4049/jimmunol.156.6.2095 · 被引用次数：312 · 研究领域：Chemokine receptors and signaling、Monoclonal and Polyclonal Antibodies Research、Immunotherapy and Immune Responses

While chemokines primarily promote chemotaxis, it is apparent that these cytokines also modulate a number of other biologic activities, including adhesion, degranulation, cytotoxicity, and enzyme release. We demonstrate here that the beta chemokines, recombinant human macrophage inflammatory protein-1 alpha and -1 beta, RANTES (regulated upon activation, normally T cell expressed and secreted), and macrophage chemotactic peptide-1, are capable of directly costimulating purified human T cell and human T cell clone proliferation and IL-2 production in the presence of anti-CD3 mAb, but not phorbol esters, in vitro. This costimulatory activity was dose and donor dependent and required the presence of free extracellular calcium as well as endogenously produced IL-2. Chemokine treatment of human T cells in vitro increased the level of cell surface CD25 and soluble CD25. In addition, these chemokines enhanced both Ag- and alloantigen-specific T cell and T cell clone proliferation. This activity was further augmented in the presence of the CD28 ligand, B7-1. Neutralization analyses using chemokine-specific Abs revealed that endogenously produced chemokines are important costimulatory mediators in human T cell activation. Together, these results suggest that chemokines not only play an important role in lymphocyte recruitment to inflammatory sites, but also participate in T cell activation.