Differential CC chemokine-induced enhancement of T helper cell cytokine production.
Chemokines are a family of small m.w. cytokines that induce chemotaxis and chemokinesis of leukocytes. These molecules are ligands for seven-transmembrane, Gi protein-linked receptors that induce a signaling cascade in human T cells and provide costimulation for T cell activation, in addition to participating in transendothelial migration of leukocytes. To address the role of chemokines in the regulation of Th cell cytokine production, we utilized an OVA-specific TCR transgenic (Tg+) model. Cells stimulated through the TCR and incubated in the presence of macrophage inflammatory protein-1alpha (MIP-1alpha) showed enhanced IFN-gamma production, whereas cells incubated in the presence of monocyte chemotactic protein-1 (MCP-1) showed enhanced IL-4 production. Similar results were obtained whether TCR Tg+ T cells were stimulated with anti-CD3 mAb or OVA peptide. Primary stimulation of T cells in the presence of chemokines, followed by secondary stimulation and tertiary stimulation with anti-TCR clonotype mAb alone (no exogenous chemokines), revealed an enhanced IFN-gamma production for MIP-1alpha stimulation and IL-4 production for MCP-1 stimulation. Naive Tg+ T cells, obtained from Tg+ mice crossed to RAG-1-deficient mice, showed enhanced IFN-gamma production when incubated with MIP-1alpha and enhanced IL-4 production when incubated with MCP-1. These results suggest CC chemokines play a role in regulating naive Th cell cytokine production, in addition to regulating leukocyte trafficking.
Karpus
W J
WJ
Department of Pathology, Northwestern University Institute for Neuroscience, Chicago, IL 60611, USA.
Lukacs
N W
NW
Kennedy
K J
KJ
Smith
W S
WS
Hurst
S D
SD
Barrett
T A
TA
D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000502:physiology*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D019402:Macrophage Inflammatory Proteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4; D007371:Interferon-gamma