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

Dennis D. Taub, Susan M. Turcovski-Corrales, Michael L. Key, Dan L. Longo, William J Murphy

Research output: Contribution to journalArticle

287 Scopus citations

Abstract

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 β chemokines, recombinant human macrophage inflammatory protein-1α and -1β, 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.

Original languageEnglish (US)
Pages (from-to)2095-2103
Number of pages9
JournalJournal of Immunology
Volume156
Issue number6
StatePublished - Mar 15 1996
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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