Activated neutrophils inhibit chemotactic migration of activated T lymphocytes to CXCL11 by multiple mechanisms

Abstract

Accumulation of T lymphocytes and neutrophils shows inversed association with the prognosis of cancer patients, suggesting infiltration of neutrophils and T cells might be differently regulated in tumor tissue. In this study, we stimulated neutrophils with PMA or LPS to produce neutrophil extracellular traps (NETs) and examined the effects on chemotactic migration of activated T cells to a representative T cell chemokine, CXCL11. Migration of the activated T cells was totally abrogated by PMA-stimulated neutrophils placed either in upper or lower chamber, which was mostly canceled by pretreatment with Catalase. Although LPS-stimulated neutrophils also inhibited T cell migration, depletion of NETs by ultracentrifugation or degradation of NETs with DNAse I restored T cell migration. Western blots showed that LPS-stimulated neutrophils thoroughly degraded CXCL11 with NETs dependent manner. Activated neutrophils inhibit T cell chemotaxis via multiple mechanisms including the release of H₂O₂ and chemokine degradation by NETs, which may suppress adaptive immunity.

Keywords: CXCL11; Chemotactic migration; Neutrophil extracellular traps; T cells.