Monocyte chemoattractant protein-1 synthesis by murine lung fibroblasts modulates CD4+ T cell activation.
This study addressed the role of endogenous monocyte chemoattractant protein-1 (MCP-1) in Ag-stimulated lymphokine synthesis and proliferation by CD4+ T cells during their coculture with purified lung fibroblasts or splenic macrophages. Initial experiments showed that fibroblasts exposed to IL-4, TNF alpha, or IL-4 and TNF-alpha (all at 10 ng/ml) for 24 h released five- to eightfold more MCP-1 than similarly treated splenic macrophages. In 72-h coculture experiments, the synthesis of IL-4 by OVA-activated CD4+ T cells added to lung fibroblasts or splenic macrophages was significantly inhibited when endogenous MCP-1 was neutralized using polyclonal anti-MCP-1 antiserum. In these same cocultures, IFN-gamma levels were significantly enhanced. Similarly, IFN-gamma levels were significantly enhanced in 72-h cocultures of a purified peptide derivative-activated CD4+ Th1 clone and lung fibroblasts or splenic macrophages following immunoneutralization of MCP-1. In separate experiments, the selective inhibition of MCP-1 synthesis by lung fibroblasts and splenic macrophages using an MCP-1 antisense oligonucleotide significantly enhanced the proliferation of CD4+ T cells during a 96-h coculture. Taken together, these data suggest that MCP-1 exerts an immunomodulatory effect on CD4+ T cell-derived IL-4 and IFN-gamma release and CD4+ T cell proliferation during cell-to-cell interactions.
Hogaboam
C M
CM
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA.
Lukacs
N W
NW
Chensue
S W
SW
Strieter
R M
RM
Kunkel
S L
SL
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000276:immunology*; D018920:Coculture Techniques; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008808:Mice, Inbred CBA; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology
D018932:Chemokine CCL2; D016376:Oligonucleotides, Antisense