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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.

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


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.


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

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