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Human peripheral γδT cell phenotypic and functional shift in response to stimulation with E.coli

Barisa, Marta; (2017) Human peripheral γδT cell phenotypic and functional shift in response to stimulation with E.coli. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

It is known that γδT cells provide immune-surveillance and host defense against infection and cancer. Our understanding of γδT cell functionality and antimicrobial immunity, however, remains poor. Limited data suggests that γδT cells can phagocytose particles and act as professional antigen-presenting cells (pAPCs). In order to examine γδT cell bacterial interactions, an ex vivo co-culture model of human peripheral blood mononuclear cell (PBMC) responses to Escherichia coli was employed. Following PBMC stimulation with E.coli, 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. Vγ9Vδ2 cell cytokine responses and cytotoxicity further presented with variable sensitivity to blocking of host butyrophilin 3A (BTN3A), in response to both, self and non-self, stimuli. We conclude that i) Vγ9Vδ2 T cells transition from early inflammatory cytotoxic killers to myeloid-like pAPCs in response to infectious stimuli, and that ii) Vγ9Vδ2 T cell recognition of targets is predominantly governed by TCR recognition of self stress markers in a BTN3A-dependent manner.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Human peripheral γδT cell phenotypic and functional shift in response to stimulation with E.coli
Event: University College London
Open access status: An open access version is available from UCL Discovery
Language: English
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10038983
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