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Front Immunol. 2018 Feb 8;9:209. doi: 10.3389/fimmu.2018.00209. eCollection 2018.

In Vitro-Generated Tc17 Cells Present a Memory Phenotype and Serve As a Reservoir of Tc1 Cells In Vivo.

Author information

1
Departamento de Biologia, Facultad de Ciencias, Universidad de Chile, Santiago, Chile.
2
Facultad de Medicina, Universidad San Sebastian, Santiago, Chile.
3
Programa de Doctorado en Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
4
Anatomy and Developmental Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
5
Fundacion Ciencia & Vida, Santiago, Chile.
6
Geroscience Center for Brain Health and Metabolism, Santiago, Chile.
7
Buck Institute for Research on Aging, Novato, CA, United States.
8
Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, CA, United States.
9
Facultad de Ciencias Biologicas, Universidad Andrés Bello, Santiago, Chile.

Abstract

Memory CD8+ T cells are ideal candidates for cancer immunotherapy because they can mediate long-term protection against tumors. However, the therapeutic potential of different in vitro-generated CD8+ T cell effector subsets to persist and become memory cells has not been fully characterized. Type 1 CD8+ T (Tc1) cells produce interferon-γ and are endowed with high cytotoxic capacity, whereas IL-17-producing CD8+ T (Tc17) cells are less cytotoxic but display enhanced self-renewal capacity. We sought to evaluate the functional properties of in vitro-generated Tc17 cells and elucidate their potential to become long lasting memory cells. Our results show that in vitro-generated Tc17 cells display a greater in vivo persistence and expansion in response to secondary antigen stimulation compared to Tc1 cells. When transferred into recipient mice, Tc17 cells persist in secondary lymphoid organs, present a recirculation behavior consistent with central memory T cells, and can shift to a Tc1 phenotype. Accordingly, Tc17 cells are endowed with a higher mitochondrial spare respiratory capacity than Tc1 cells and express higher levels of memory-related molecules than Tc1 cells. Together, these results demonstrate that in vitro-generated Tc17 cells acquire a central memory program and provide a lasting reservoir of Tc1 cells in vivo, thus supporting the use of Tc17 lymphocytes in the design of novel and more effective therapies.

KEYWORDS:

CD8+ T cell memory; Tc17 cells; homing; oxidative metabolism; persistence; secondary expansion

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