Chemokines and T lymphocyte activation: I. Beta chemokines costimulate human T lymphocyte activation in vitro.
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.
Taub
D D
DD
Clinical Services, Science Applications International Corporation-Frederick, MD 21702, USA.
Turcovski-Corrales
S M
SM
Key
M L
ML
Longo
D L
DL
Murphy
W J
WJ
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D002118:Calcium / Q000502:physiology; D054407:Chemokine CCL4; D018925:Chemokines / Q000145:classification / Q000494:pharmacology*; D002999:Clone Cells; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000502:physiology; D007399:Interphase / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D019402:Macrophage Inflammatory Proteins; D008264:Macrophages / Q000276:immunology; D015846:Monokines / Q000276:immunology / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D054407:Chemokine CCL4; D018925:Chemokines; D007376:Interleukin-2; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D015375:Receptors, Interleukin-2; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium