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Poster Display session 1

5400 - Tr1-like cells in human peripheral blood are part of the T effector memory pool and are preferentially stimulated via CD55

Date

28 Sep 2019

Session

Poster Display session 1

Presenters

Iniobong Charles

Citation

Annals of Oncology (2019) 30 (suppl_5): v1-v24. 10.1093/annonc/mdz238

Authors

I.A. Charles, J.M. Ramage, I. Spendlove

Author affiliations

  • Academic Oncology, City Hospital Campus - Nottingham University Hospitals NHS Trust, NG5 1PB - Nottingham/GB
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Resources

Abstract 5400

Background

Type 1 regulatory (Tr1) T cells, like every effector T cells, arise from stimulation of naïve T cell precursor and enter a long term memory pool. While they can adapt their function to specific environmental cues, sometimes called plasticity, their phenotype remains broadly fixed. Unlike natural T regulator cells that emerge from the thymus with a defined phenotype (CD4+CD25hiCD127loFoxP3+), there is uncertainty over the characterisation of inducible Tr1 cells.

Methods

In this study we stimulated human total CD4+ T cells with PMA/ Ionomycin and also demonstrated that these cells respond specifically to costimulation via CD97-CD55. Dual cell surface capture (CSA) was used to assay for IL-10 and IFN-γ and intracellular staining for Tr1 markers.

Results

A small (<5%) population were IL-10+ IL-4-, IFN-γ- and expressed other markers commonly associated with Tr1-like cells. These included; CD49b, LAG-3, CD226, PD-1, CTLA-4, and TIM-3. However they were negative for FoxP3 expression, and expressed Cmaf, which is thought to be responsible for the transcriptional events within this population. Furthermore, we show that these Tr1-like cells form part of the immunological memory and reside predominantly within the effector memory (CD62L- CD45RO+, TEM) pool. Unlike the majority of other studies where Tr1 is generated by chronic stimulation of PBMCs in the presence of recombinant IL-10 for several days, as far as we are aware, this is the first report characterising Tr1 directly ex vivo from human peripheral blood.

Conclusions

We have also demonstrated that these cells respond specifically to costimulation via CD97-CD55 to drive proliferation and maintain the IL-10 single positive, Tr1 phenotype outlined above. This supports the idea that once differentiated from naïve precursors, Tr1-like cells respond to CD55 costimulation to maintain a small (<5%) pool with a committed IL-10+ IL-4-IFN-γ- phenotype.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The University of Nottingham.

Funding

The Commonwealth Scholarships Commission, London.

Disclosure

All authors have declared no conflicts of interest.

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