Differential CC chemokine-induced enhancement of T helper cell cytokine production

• Published in: The Journal of immunology (1950) Vol. 158; no. 9; pp. 4129 - 4136
• Main Authors: Karpus, WJ, Lukacs, NW, Kennedy, KJ, Smith, WS, Hurst, SD, Barrett, TA
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.05.1997
• Subjects: Animals; Cell Survival; Cells, Cultured; Chemokine CCL2 - physiology; Chemokine CCL3; Chemokine CCL4; Immunologic Memory; Interferon-gamma - biosynthesis; Interleukin-4 - biosynthesis; Macrophage Inflammatory Proteins - physiology; Mice; Mice, Inbred BALB C; Mice, Transgenic; Receptors, Antigen, T-Cell - physiology; T-Lymphocytes, Helper-Inducer - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.158.9.4129

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.