Expansion and CD2/CD3/CD28 stimulation enhance Th2 cytokine secretion of human invariant NKT cells with retained anti-tumor cytotoxicity.

Antibodies / pharmacology Apoptosis / drug effects Blood Donors CD2 Antigens / immunology CD28 Antigens / immunology CD3 Complex / immunology Cell Proliferation / drug effects Cell Transplantation / methods Cells, Cultured Cytokines / metabolism Gene Expression Profiling Humans Immunotherapy / methods Jurkat Cells K562 Cells Lymphocyte Activation / immunology Natural Killer T-Cells / immunology Th2 Cells / immunology
NKT cells co-stimulation cytotoxicity iNKT cells immunotherapy leukemia regulatory T cells transplantation

Journal

Cytotherapy
ISSN: 1477-2566
Titre abrégé: Cytotherapy
Pays: England
ID NLM: 100895309

Informations de publication

Date de publication:
05 2020
Historique:
received: 26 05 2019
revised: 14 01 2020
accepted: 22 01 2020
pubmed: 3 4 2020
medline: 28 10 2020
entrez: 3 4 2020
Statut: ppublish

Résumé

Key obstacles in human iNKT cell translational research and immunotherapy include the lack of robust protocols for dependable expansion of human iNKT cells and the paucity of data on phenotypes in post-expanded cells. We delineate expansion methods using interleukin (IL)-2, IL-7 and allogeneic feeder cells and anti-CD2/CD3/CD28 stimulation by which to dependably augment Th2 polarization and direct cytotoxicity of human peripheral blood CD3 Gene and protein expression profiling demonstrated augmented Th2 cytokine secretion (IL-4, IL-5, IL-13) in expanded iNKT cells stimulated with anti-CD2/CD3/CD28 antibodies. Cytotoxic effector molecules including granzyme B were increased in expanded iNKT cells after CD2/CD3/CD28 stimulation. Direct cytotoxicity assays using unstimulated expanded iNKT cell effectors revealed α-galactosyl ceramide (α-GalCer)-dependent killing of the T-ALL cell line Jurkat. Moreover, CD2/CD3/CD28 stimulation of expanded iNKT cells augmented their (α-GalCer-independent) killing of Jurkat cells. Co-culture of expanded iNKT cells with stimulated responder cells confirmed contact-dependent inhibition of activated CD4 These data establish a robust protocol to expand and novel pathways to enhance Th2 cytokine secretion and direct cytotoxicity in human iNKT cells, findings with direct implications for autoimmunity, vaccine augmentation and anti-infective immunity, cancer immunotherapy and transplantation.

Sections du résumé

BACKGROUND AIMS
Key obstacles in human iNKT cell translational research and immunotherapy include the lack of robust protocols for dependable expansion of human iNKT cells and the paucity of data on phenotypes in post-expanded cells.
METHODS
We delineate expansion methods using interleukin (IL)-2, IL-7 and allogeneic feeder cells and anti-CD2/CD3/CD28 stimulation by which to dependably augment Th2 polarization and direct cytotoxicity of human peripheral blood CD3
RESULTS
Gene and protein expression profiling demonstrated augmented Th2 cytokine secretion (IL-4, IL-5, IL-13) in expanded iNKT cells stimulated with anti-CD2/CD3/CD28 antibodies. Cytotoxic effector molecules including granzyme B were increased in expanded iNKT cells after CD2/CD3/CD28 stimulation. Direct cytotoxicity assays using unstimulated expanded iNKT cell effectors revealed α-galactosyl ceramide (α-GalCer)-dependent killing of the T-ALL cell line Jurkat. Moreover, CD2/CD3/CD28 stimulation of expanded iNKT cells augmented their (α-GalCer-independent) killing of Jurkat cells. Co-culture of expanded iNKT cells with stimulated responder cells confirmed contact-dependent inhibition of activated CD4
DISCUSSION
These data establish a robust protocol to expand and novel pathways to enhance Th2 cytokine secretion and direct cytotoxicity in human iNKT cells, findings with direct implications for autoimmunity, vaccine augmentation and anti-infective immunity, cancer immunotherapy and transplantation.

Identifiants

DOI: 10.1016/j.jcyt.2020.01.011 PMID: 32238299 PMC: PMC7666372
pubmed: 32238299
pii: S1465-3249(20)30015-3
doi: 10.1016/j.jcyt.2020.01.011
pmc: PMC7666372
mid: NIHMS1569140
pii:
doi:

Substances chimiques

Antibodies 0
CD2 Antigens 0
CD28 Antigens 0
CD3 Complex 0
Cytokines 0

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

276-290

Subventions

Organisme : NCI NIH HHS
ID : P30 CA021765
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL133462
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA240139
Pays : United States

Informations de copyright

Copyright © 2020 International Society for Cell and Gene Therapy. Published by Elsevier Inc. All rights reserved.

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Auteurs

Kelly Andrews (K)

Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee, USA; Departments of Pediatrics and Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida, USA; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, USA.

Anouk A J Hamers (AAJ)

Departments of Pediatrics and Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida, USA; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, USA.

Xiaodian Sun (X)

Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, USA.

Geoffrey Neale (G)

Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

Katherine Verbist (K)

Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

Paige Tedrick (P)

Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

Kim E Nichols (KE)

Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

Shalini Pereira (S)

Scisco Genetics Inc., Seattle, Washington, USA.

Daniel E Geraghty (DE)

Scisco Genetics Inc., Seattle, Washington, USA; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

Asha B Pillai (AB)

Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee, USA; Departments of Pediatrics and Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida, USA; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, USA. Electronic address: asha.pillai@med.miami.edu.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Expansion and CD2/CD3/CD28 stimulation enhance...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Mort cellulaire › Mort cellulaire régulée › Apoptose › Expansion and CD2/CD3/CD28 stimulation enhance...
questionsmedicales.fr › Personnes › Donneurs de tissus › Donneurs de sang › Expansion and CD2/CD3/CD28 stimulation enhance...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Antigènes de différenciation › Antigènes de différenciation des lymphocytes T › Antigènes CD2 › Expansion and CD2/CD3/CD28 stimulation enhance...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Antigènes de différenciation › Antigènes de différenciation des lymphocytes T › Antigène CD28 › Expansion and CD2/CD3/CD28 stimulation enhance...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Antigènes de différenciation › Antigènes de différenciation des lymphocytes T › Antigènes CD3 › Expansion and CD2/CD3/CD28 stimulation enhance...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › Expansion and CD2/CD3/CD28 stimulation enhance...
questionsmedicales.fr › Procédures de chirurgie opératoire › Transplantation › Transplantation cellulaire › Expansion and CD2/CD3/CD28 stimulation enhance...
questionsmedicales.fr › Cellules › Cellules cultivées › Expansion and CD2/CD3/CD28 stimulation enhance...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Expansion and CD2/CD3/CD28 stimulation enhance...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de profil d'expression de gènes › Expansion and CD2/CD3/CD28 stimulation enhance...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Expansion and CD2/CD3/CD28 stimulation enhance...
questionsmedicales.fr › Thérapeutique › Biothérapie › Immunothérapie › Expansion and CD2/CD3/CD28 stimulation enhance...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Cellules Jurkat › Expansion and CD2/CD3/CD28 stimulation enhance...
questionsmedicales.fr › Cellules › Cellules érythroïdes › Cellules K562 › Expansion and CD2/CD3/CD28 stimulation enhance...
questionsmedicales.fr › Phénomènes du système immunitaire › Activation des lymphocytes › Expansion and CD2/CD3/CD28 stimulation enhance...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Cellules T tueuses naturelles › Expansion and CD2/CD3/CD28 stimulation enhance...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Sous-populations de lymphocytes T › Lymphocytes T auxiliaires › Lymphocytes auxiliaires Th2 › Expansion and CD2/CD3/CD28 stimulation enhance...