Human mast cells release Interleukin‐8 and induce neutrophil chemotaxis on contact with activated T cells

Background: Mast cells have recently been shown to control neutrophil recruitment during T‐cell mediated cutaneous DTH reaction in vivo through TNF‐α and MIP‐2, the functional murine analogue of human IL‐8. Although the nature of signals transmitted from T cells which activate mast cells has not yet been defined, we hypothesized that a direct cross‐talk (i.e. heterotypic adhesion) between these two cell populations exists, as has previously been reported. Aims: The present study was aimed at gaining insight into the functional role of mast cell–T cell contact in expression and release of IL‐8, and its effect on neutrophil chemotaxis. Methods: The IL‐8 gene expression was identified by Affymetrix GeneChip arrays, validated by RT‐PCR and the protein measured by ELISA. Chemotaxis was evaluated by using a modified Boyden chamber assay. Results: Mast cells were found to express and release significantly higher concentrations of IL‐8 on incubation with membranes obtained from activated, as compared to resting T cells. Supernatants obtained from these activated mast cells induced significant neutrophil chemotaxis that was inhibited by neutralizing mAb to IL‐8. Conclusions: Thus, activated T cells, on heterotypic adhesion to mast cells, deliver the necessary signals for the latter to release cytokines and chemokines necessary for cell migration to sites of antigen challenge, thereby facilitating T‐cell mediated inflammatory processes.