Differential Role of “Signal 3” Inflammatory Cytokines in Regulating CD8 T Cell Expansion and Differentiation in vivo

Following an infection, naïve CD8 T cells are stimulated by dendritic cells (DC) displaying pathogen-derived peptides on MHC class I molecules (signal 1) and costimulatory molecules (signal 2). Additionally, pathogen-induced inflammatory cytokines also act directly on the responding CD8 T cells to r...

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Autores principales: Pham, Nhat-Long L., Badovinac, Vladimir P., Harty, John T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Research Foundation 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342074/
https://www.ncbi.nlm.nih.gov/pubmed/22566795
http://dx.doi.org/10.3389/fimmu.2011.00004
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author Pham, Nhat-Long L.
Badovinac, Vladimir P.
Harty, John T.
author_facet Pham, Nhat-Long L.
Badovinac, Vladimir P.
Harty, John T.
author_sort Pham, Nhat-Long L.
collection PubMed
description Following an infection, naïve CD8 T cells are stimulated by dendritic cells (DC) displaying pathogen-derived peptides on MHC class I molecules (signal 1) and costimulatory molecules (signal 2). Additionally, pathogen-induced inflammatory cytokines also act directly on the responding CD8 T cells to regulate their expansion and differentiation. In particular, both type I interferons (IFNs) and IL-12 have been described as critical survival signals (signal 3) for optimal CD8 T cell accumulation during the expansion phase. Furthermore, expansion in numbers of antigen-specific CD8 T cells is coupled with their acquisition of effector functions to combat the infection. However, it still remains unclear whether these same cytokines also regulate the effector/memory differentiation program of the CD8 T cell response in vivo. Here, we demonstrate that defective signaling by either type I IFNs or IL-12 to the responding CD8 T cells impairs maximal expansion in response to DC immunization + CpG ODN, but neither of these cytokines is essential to regulate the effector/memory differentiation program. In addition, lack of direct IL-12 signaling to CD8 T cells accelerates the development of central memory phenotype in both primary and secondary antigen-specific memory CD8 T cells.
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spelling pubmed-33420742012-05-07 Differential Role of “Signal 3” Inflammatory Cytokines in Regulating CD8 T Cell Expansion and Differentiation in vivo Pham, Nhat-Long L. Badovinac, Vladimir P. Harty, John T. Front Immunol Immunology Following an infection, naïve CD8 T cells are stimulated by dendritic cells (DC) displaying pathogen-derived peptides on MHC class I molecules (signal 1) and costimulatory molecules (signal 2). Additionally, pathogen-induced inflammatory cytokines also act directly on the responding CD8 T cells to regulate their expansion and differentiation. In particular, both type I interferons (IFNs) and IL-12 have been described as critical survival signals (signal 3) for optimal CD8 T cell accumulation during the expansion phase. Furthermore, expansion in numbers of antigen-specific CD8 T cells is coupled with their acquisition of effector functions to combat the infection. However, it still remains unclear whether these same cytokines also regulate the effector/memory differentiation program of the CD8 T cell response in vivo. Here, we demonstrate that defective signaling by either type I IFNs or IL-12 to the responding CD8 T cells impairs maximal expansion in response to DC immunization + CpG ODN, but neither of these cytokines is essential to regulate the effector/memory differentiation program. In addition, lack of direct IL-12 signaling to CD8 T cells accelerates the development of central memory phenotype in both primary and secondary antigen-specific memory CD8 T cells. Frontiers Research Foundation 2011-02-11 /pmc/articles/PMC3342074/ /pubmed/22566795 http://dx.doi.org/10.3389/fimmu.2011.00004 Text en Copyright © 2011 Pham, Badovinac and Harty. http://www.frontiersin.org/licenseagreement This is an open-access article subject to an exclusive license agreement between the authors and Frontiers Media SA, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.
spellingShingle Immunology
Pham, Nhat-Long L.
Badovinac, Vladimir P.
Harty, John T.
Differential Role of “Signal 3” Inflammatory Cytokines in Regulating CD8 T Cell Expansion and Differentiation in vivo
title Differential Role of “Signal 3” Inflammatory Cytokines in Regulating CD8 T Cell Expansion and Differentiation in vivo
title_full Differential Role of “Signal 3” Inflammatory Cytokines in Regulating CD8 T Cell Expansion and Differentiation in vivo
title_fullStr Differential Role of “Signal 3” Inflammatory Cytokines in Regulating CD8 T Cell Expansion and Differentiation in vivo
title_full_unstemmed Differential Role of “Signal 3” Inflammatory Cytokines in Regulating CD8 T Cell Expansion and Differentiation in vivo
title_short Differential Role of “Signal 3” Inflammatory Cytokines in Regulating CD8 T Cell Expansion and Differentiation in vivo
title_sort differential role of “signal 3” inflammatory cytokines in regulating cd8 t cell expansion and differentiation in vivo
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342074/
https://www.ncbi.nlm.nih.gov/pubmed/22566795
http://dx.doi.org/10.3389/fimmu.2011.00004
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