Chemokines as regulators of T cell differentiation.
Chemokines play well established roles as attractants of naïve and effector T cells. New studies indicate that chemokines also have roles in regulating T cell differentiation. Blocking Gi protein-coupled receptor signaling by pertussis toxin as well as deficiencies in G alpha 12, chemokine receptor 2 (CCR2), CCR5, chemokine ligand 2 (CCL2, also known as monocyte chemoattractant protein 1, or MCP-1), CCL3 (macrophage inflammatory protein 1 alpha, or MIP-1 alpha) and CCL5 (RANTES) have all been found to have effects on the magnitude and cytokine polarity of the T cell response. Here we focus on findings in the CCL2-CCR2 and CCL3-CCR5 ligand-receptor systems. The roles of these molecules in regulating T cell fate include possible indirect effects on antigen-presenting cells and direct effects on differentiating T cells. Models to account for the action of chemokines and G protein-coupled receptor signals in regulating T cell differentiation are discussed.
Luther
S A
SA
Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California San Francisco, 513 Parnassus Ave., San Francisco, CA 94143-0414, USA. sluther@itsa.ucsf.edu
Cyster
J G
JG
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D018925:Chemokines / Q000276:immunology*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis; D008024:Ligands; D008954:Models, Biological; D054389:Receptors, CCR1; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000276:immunology / Q000378:metabolism; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
C515300:CCR1 protein, human; C515334:CCR2 protein, human; D018925:Chemokines; D008024:Ligands; D054389:Receptors, CCR1; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D018664:Interleukin-12; D019206:GTP-Binding Protein alpha Subunits, Gi-Go