Journal of Clinical and Cellular Immunology
Open Access

Transforming growth factor-β programs central-memory differentiation in ex vivo stimulated human T cells by modulating ID3 expression

6^th International Conference and Expo on Immunology

October 24-26, 2016 Chicago, USA

Amina Dahmani, Cedric Carli, Manon Richaud, Valerie Janelle, Myriam Khalili, Mathieu Goupil and Jean-Sebastien Delisle

University of Montreal, Canada

Posters & Accepted Abstracts: J Clin Cell Immunol

Abstract :

Adoptive immunotherapy (AI) has emerged as a potentially curative therapy for advanced cancer and infections. Recent findings suggest that the transfer of T-cells with â�?�?earlyâ�? memory features may improve the therapeutic potential of AI. TGF-�?² is a pleiotropic cytokine that controls a large spectrum of biological and pathological processes. In T-cell biology, TGF-�?² is mostly known for its immunoregulatory properties, but recent evidence has revealed a novel role of TGF-�?² in T-cell memory differentiation and maintenance. Thus, we investigated whether TGF-�?² could promote features of memory in ex vivo stimulated human T-cells to further improve the efficacy of clinical protocols for AI. Here we show that agonistic TGF-�?² stimulation leads to the expression of central memory markers without significantly altering T-cell expansion or polyfunctional cytokine secretion following stimulation. Furthermore, TGF-�?² exposure decreased expression of transcription factors responsible for effector differentiation (T-BET, GATA3 and BLIMP1) and increased those associated with memory differentiation, notably ID3. The knock-down of ID3 by specific siRNA revealed that TGF-�?²-driven T-cell memory differentiation largely depends on ID3. Moreover, TGF-�?²-exposed T-cells showed enhanced persistence, expansion and alloreactivity after adoptive transfer into NSG mice. Finally, using clinically relevant culture methods to generate T-cell lines against viral and tumor antigens, we found that TGF-�?² programmed the expression of early memory markers without significantly curtailing T-cell expansion or antigenspecificity. This finding provides a rationale for clinical use of TGF-�?² to optimize memory phenotype of ex vivo pathogen/ antigen-specific T-cells expanded for AI.

Biography :

Email: amina.dahmani1@gmail.com