Role of Monocyte Chemotactic Protein-1/CC Chemokine Ligand 2 on γδ T Lymphocyte Trafficking during Inflammation Induced by Lipopolysaccharide orMycobacterium bovisBacille Calmette-Guérin

Abstract

γδ T lymphocytes are involved in a great variety of inflammatory and infectious responses. However, the mechanisms by which γδ T lymphocytes migrate to inflamed sites are poorly understood. In this study we investigate the role of monocyte chemotactic protein (MCP)-1 in regulating γδ T cell migration after LPS or Mycobacterium bovis bacille Calmette-Guérin (BCG) challenge. LPS-induced γδ T cell influx was significantly inhibited by either pretreatment with dexamethasone or vaccinia virus Lister 35-kDa chemokine binding protein, vCKBP, a CC chemokine neutralizing protein, suggesting a role for CC chemokines in this phenomenon. LPS stimulation increased the expression of MCP-1 mRNA and protein at the inflammation site within 6 h. It is noteworthy that LPS was unable to increase MCP-1 production or γδ T cell recruitment in C3H/HeJ, indicative of the involvement of Toll-like receptor 4. γδ T cells express MCP-1 receptor CCR2. Pretreatment with anti-MCP-1 mAb drastically inhibited LPS-induced in vivo γδ T cell mobilization. Indeed, MCP-1 knockout mice were unable to recruit γδ T cells to the pleural cavity after LPS stimulation, effect that could be restored by coadministration of MCP-1. In addition, BCG-induced γδ lymphocyte accumulation was significantly reduced in MCP-1 knockout mice when compared with wild-type mice. In conclusion, our results indicate that LPS-induced γδ T lymphocyte migration is dependent on Toll-like receptor 4 and sensitive to both dexamethasone and CC chemokine-binding protein inhibition. Moreover, by using MCP-1 neutralizing Abs and genetically deficient mice we show that LPS- and BCG-induced γδ T lymphocyte influx to the pleural cavity of mice is mainly orchestrated by the CC chemokine MCP-1.

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