2026-06-14T05:05:19Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/89592024-09-27T23:16:22Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud
author
Aragoneses-Fenoll, Laura
author
Ojeda, Gloria
author
Montes-Casado, Maria
author
Acosta-Ampudia, Yeny
author
Dianzani, Umberto
author
Portoles, Pilar
author
Rojo, José M
funder
Ministerio de Economía, Industria y Competitividad (España)
funder
Italian Association for Cancer Research
2020-01-29T11:43:40Z
2020-01-29T11:43:40Z
2018
Front Immunol. 2018 Feb 27;9:332.
10.3389/fimmu.2018.00332
1664-3224
Frontiers in immunology
29535720
http://hdl.handle.net/20.500.12105/8959
Class IA phosphatidylinositol 3-kinase (PI3K) catalytic subunits p110α and p110δ are targets in cancer therapy expressed at high levels in T lymphocytes. The role of p110δ PI3K in normal or pathological immune responses is well established, yet the importance of p110α subunits in T cell-dependent immune responses is not clear. To address this problem, mice with p110α conditionally deleted in CD4+ and CD8+ T lymphocytes (p110α-/-ΔT) were used. p110α-/-ΔT mice show normal development of T cell subsets, but slightly reduced numbers of CD4+ T cells in the spleen. "In vitro," TCR/CD3 plus CD28 activation of naive CD4+ and CD8+ p110α-/-ΔT T cells showed enhanced effector function, particularly IFN-γ secretion, T-bet induction, and Akt, Erk, or P38 activation. Tfh derived from p110α-/-ΔT cells also have enhanced responses when compared to normal mice, and IL-2 expanded p110α-/-ΔT CD8+ T cells had enhanced levels of LAMP-1 and Granzyme B. By contrast, the expansion of p110α-/-ΔT iTreg cells was diminished. Also, p110α-/-ΔT mice had enhanced anti-keyhole limpet hemocyanin (KLH) IFN-γ, or IL-4 responses and IgG1 and IgG2b anti-KLH antibodies, using CFA or Alum as adjuvant, respectively. When compared to WT mice, p110α-/-ΔT mice inoculated with B16.F10 melanoma showed delayed tumor progression. The percentage of CD8+ T lymphocytes was higher and the percentage of Treg cells lower in the spleen of tumor-bearing p110α-/-ΔT mice. Also, IFN-γ production in tumor antigen-activated spleen cells was enhanced. Thus, PI3K p110α plays a significant role in antigen activation and differentiation of CD4+ and CD8+ T lymphocytes modulating antitumor immunity.
eng
CD28 costimulation
PI3-kinase alpha subunit
PI3K
T lymphocytes
Anti-KLH response
Melanoma
T-Cell-Specific Loss of the PI-3-Kinase p110α Catalytic Subunit Results in Enhanced Cytokine Production and Antitumor Response
journal article
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TCellSpecificLoss_2018.pdf
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TCellSpecificLoss_2018.pdf.txt