In vitro-generated Tc17 cells present a memory phenotype and serve as a reservoir of Tc1 cells in vivo

Felipe Flores-Santibáñez, Bárbara Cuadra, Dominique Fernández, Mariana V. Rosemblatt, Sarah Núñez, Pablo Cruz, Felipe Gálvez-Cancino, J. César Cárdenas, Alvaro Lladser, Mario Rosemblatt, María Rosa Bono, Daniela Sauma

Resultado de la investigación: Article

3 Citas (Scopus)

Resumen

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.

Idioma originalEnglish
Número de artículo209
PublicaciónFrontiers in Immunology
Volumen9
N.ºFEB
DOI
EstadoPublished - 8 feb 2018

Huella dactilar

Phenotype
In Vitro Techniques
T-Lymphocytes
Interleukin-17
T-Lymphocyte Subsets
Immunotherapy
Interferons
Neoplasms
Lymphocytes
Antigens
Therapeutics

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Citar esto

Flores-Santibáñez, F., Cuadra, B., Fernández, D., Rosemblatt, M. V., Núñez, S., Cruz, P., ... Sauma, D. (2018). In vitro-generated Tc17 cells present a memory phenotype and serve as a reservoir of Tc1 cells in vivo. Frontiers in Immunology, 9(FEB), [209]. https://doi.org/10.3389/fimmu.2018.00209
Flores-Santibáñez, Felipe ; Cuadra, Bárbara ; Fernández, Dominique ; Rosemblatt, Mariana V. ; Núñez, Sarah ; Cruz, Pablo ; Gálvez-Cancino, Felipe ; César Cárdenas, J. ; Lladser, Alvaro ; Rosemblatt, Mario ; Bono, María Rosa ; Sauma, Daniela. / In vitro-generated Tc17 cells present a memory phenotype and serve as a reservoir of Tc1 cells in vivo. En: Frontiers in Immunology. 2018 ; Vol. 9, N.º FEB.
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title = "In vitro-generated Tc17 cells present a memory phenotype and serve as a reservoir of Tc1 cells in vivo",
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.",
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Flores-Santibáñez, F, Cuadra, B, Fernández, D, Rosemblatt, MV, Núñez, S, Cruz, P, Gálvez-Cancino, F, César Cárdenas, J, Lladser, A, Rosemblatt, M, Bono, MR & Sauma, D 2018, 'In vitro-generated Tc17 cells present a memory phenotype and serve as a reservoir of Tc1 cells in vivo', Frontiers in Immunology, vol. 9, n.º FEB, 209. https://doi.org/10.3389/fimmu.2018.00209

In vitro-generated Tc17 cells present a memory phenotype and serve as a reservoir of Tc1 cells in vivo. / Flores-Santibáñez, Felipe; Cuadra, Bárbara; Fernández, Dominique; Rosemblatt, Mariana V.; Núñez, Sarah; Cruz, Pablo; Gálvez-Cancino, Felipe; César Cárdenas, J.; Lladser, Alvaro; Rosemblatt, Mario; Bono, María Rosa; Sauma, Daniela.

En: Frontiers in Immunology, Vol. 9, N.º FEB, 209, 08.02.2018.

Resultado de la investigación: Article

TY - JOUR

T1 - In vitro-generated Tc17 cells present a memory phenotype and serve as a reservoir of Tc1 cells in vivo

AU - Flores-Santibáñez, Felipe

AU - Cuadra, Bárbara

AU - Fernández, Dominique

AU - Rosemblatt, Mariana V.

AU - Núñez, Sarah

AU - Cruz, Pablo

AU - Gálvez-Cancino, Felipe

AU - César Cárdenas, J.

AU - Lladser, Alvaro

AU - Rosemblatt, Mario

AU - Bono, María Rosa

AU - Sauma, Daniela

PY - 2018/2/8

Y1 - 2018/2/8

N2 - 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.

AB - 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.

KW - CD8+ T cell memory

KW - Homing

KW - Oxidative metabolism

KW - Persistence

KW - Secondary expansion

KW - Tc17 cells

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U2 - 10.3389/fimmu.2018.00209

DO - 10.3389/fimmu.2018.00209

M3 - Article

AN - SCOPUS:85041863841

VL - 9

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

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Flores-Santibáñez F, Cuadra B, Fernández D, Rosemblatt MV, Núñez S, Cruz P y otros. In vitro-generated Tc17 cells present a memory phenotype and serve as a reservoir of Tc1 cells in vivo. Frontiers in Immunology. 2018 feb 8;9(FEB). 209. https://doi.org/10.3389/fimmu.2018.00209