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Suppression of inducible CD4 regulatory cells by MHC class I-restricted human tumor epitope specific TCR engineered multifunctional CD4 T cells.
- Source :
-
Human immunology [Hum Immunol] 2016 Oct; Vol. 77 (10), pp. 905-911. Date of Electronic Publication: 2016 Jun 16. - Publication Year :
- 2016
-
Abstract
- Regulatory T cells (Treg) can interfere with the generation and function of anti-tumor immune effectors. Accordingly, ways that could block Treg function would be useful in cancer immunotherapy. We have previously shown that incorporation of CD4+CD25-ve T cells in an in vitro cytolytic T lymphocyte (CTL) generation assay leads to generation of induced regulatory T cells (iTregs), and that these iTreg block the generation of productive CTL response (Chattopadhyay et al., 2006). We here show that human CD4 T cells engineered to express MHC class I-restricted human melanoma associated epitope, MART-127-35, specific T cell receptor (TCR), that can simultaneously exhibit helper as well as cytolytic effector functions (Chhabra et al., 2008, Ray et al., 2010), can interfere with the generation of inducible Treg, block iTreg-mediated suppression, and allow the activation and expansion of MART-127-35 specific CTL responses, in vitro. We also show that mitigation of Treg generation by TCR engineered CD4 T cells is not mediated by a soluble factor and may involve "licensing/conditioning" of the dendritic cells (DC). Our data offer novel insights on the biology of MHC class I restricted TCReng CD4 T cells and have translational implications.<br /> (Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Cells, Cultured
Dendritic Cells immunology
Epitopes immunology
Genetic Engineering
Histocompatibility Antigens Class I metabolism
Immunosuppression Therapy
Lymphocyte Activation
Melanoma immunology
Neoplasm Proteins immunology
T-Cell Antigen Receptor Specificity genetics
Tumor Escape
Epitopes metabolism
Immunotherapy methods
Melanoma metabolism
Neoplasm Proteins metabolism
Receptors, Antigen, T-Cell genetics
T-Lymphocytes, Cytotoxic physiology
T-Lymphocytes, Helper-Inducer physiology
T-Lymphocytes, Regulatory physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-1166
- Volume :
- 77
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Human immunology
- Publication Type :
- Academic Journal
- Accession number :
- 27320826
- Full Text :
- https://doi.org/10.1016/j.humimm.2016.06.011