Abstract

γδT cells provide immune-surveillance and host defense against infection and cancer. Surprisingly, functional details of γδT cell antimicrobial immunity to infection remain largely unexplored. Limited data suggests that γδT cells can phagocytose particles and act as professional antigen-presenting cells (pAPC). These potential functions, however, remain controversial. To better understand γδT cell-bacterial interactions, an ex vivo co-culture model of human peripheral blood mononuclear cell (PBMC) responses to Escherichia coli was employed. Vγ9Vδ2 cells underwent rapid T cell receptor (TCR)-dependent proliferation and functional transition from cytotoxic, inflammatory cytokine immunity, to cell expansion with diminished cytokine but increased costimulatory molecule expression, and capacity for professional phagocytosis. Phagocytosis was augmented by IgG opsonization, and inhibited by TCR-blockade, suggesting a licensing interaction involving the TCR and FcγR. Vγ9Vδ2 cells displayed potent cytotoxicity through TCR-dependent and independent mechanisms. We conclude that γδT cells transition from early inflammatory cytotoxic killers to myeloid-like APC in response to infectious stimuli.

Highlights

  • ΓδT cells express a T cell receptor (TCR) composed of γ and δ chains, and constitute 1–15% of human peripheral blood mononuclear cells (PBMC); and up to 40% of intraepithelial lymphocytes in epithelial linings[1]

  • The in vivo observations of γδT cell expansion in clinical infectious disease, and the ex vivo exploration of human γδT cell professional antigen-presenting cells (pAPC) function and phagocytosis by Brandes et al and our own laboratory[22,23,24], prompted us to investigate how Gram-negative bacteria may modulate the plasticity of this unique T cell population

  • We explored the impact of cell expansion on γδT cell phagocytic capacity in detail. 14 day zoledronic acid-expanded γδT cells were co-cultured with protease-activated DQ-Green fluorescent, bovine serum albumin (BSA)labeled polystyrene beads (0.5 μm or 1.0 μm in size), with or without IgG opsonization

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Summary

Introduction

ΓδT cells express a T cell receptor (TCR) composed of γ and δ chains, and constitute 1–15% of human peripheral blood mononuclear cells (PBMC); and up to 40% of intraepithelial lymphocytes in epithelial linings[1]. Evidence suggests that the predominant human peripheral γδT cell subset, with a Vγ9Vδ2 TCR, is involved in immuno-surveillance of stress signals emanating from endogenous (e.g. tumor cells) and microbial pyrophosphates (e.g. infected cells)[3]. Significant increase in systemic and mucosal γδT cells is seen in several acute infectious diseases. E. coli, a causative agent of human sepsis and bacteremia, expresses phosphoantigens that are documented potent activators of peripheral Vγ9Vδ2 γδT cells[19, 25].

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