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Memory CD8+ T cells require CD28 costimulation
Journal article   Open access   Peer reviewed

Memory CD8+ T cells require CD28 costimulation

Annie B Borowski, Alina C Boesteanu, Yvonne M Mueller, Caterina Carafides, David J Topham, John D Altman, Stephen R Jennings and Peter D Katsikis
The Journal of immunology (1950), v 179(10), pp 6494-6503
15 Nov 2007
DOI: https://doi.org/10.4049/jimmunol.179.10.6494
PMID: 17982038
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.4049/jimmunol.179.10.6494View
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Abstract

Proto-Oncogene Proteins c-bcl-2 - immunology CD28 Antigens - immunology HIV - immunology Measles virus - immunology Mice, Knockout CD4-Positive T-Lymphocytes - immunology Cancer Vaccines - immunology Animals Neoplasms - immunology Cell Cycle - immunology Female Herpesvirus 1, Human - immunology Immunologic Memory Influenza A virus - immunology Mice CD8-Positive T-Lymphocytes - immunology Viral Vaccines - immunology Orthomyxoviridae Infections - immunology Herpesviridae Infections - immunology Tumor Escape - immunology
CD8(+) T cells are a critical component of the adaptive immune response against infections and tumors. A current paradigm in immunology is that naive CD8(+) T cells require CD28 costimulation, whereas memory CD8(+) T cells do not. We show here, however, that during viral infections of mice, costimulation is required in vivo for the reactivation of memory CD8(+) T cells. In the absence of CD28 costimulation, secondary CD8(+) T cell responses are greatly reduced and this impairs viral clearance. The failure of CD8(+) T cells to expand in the absence of CD28 costimulation is CD4(+) T cell help independent and is accompanied by a failure to down-regulate Bcl-2 and by cell cycle arrest. This requirement for CD28 costimulation was shown in both influenza A and HSV infections. Thus, contrary to current dogma, memory CD8(+) T cells require CD28 costimulation to generate maximal secondary responses against pathogens. Importantly, this CD28 requirement was shown in the context of real infections were multiple other cytokines and costimulators may be up-regulated. Our findings have important implications for pathogens, such as HIV and measles virus, and tumors that evade the immune response by failing to provide CD28 costimulation. These findings also raise questions about the efficacy of CD8(+) T cell-based vaccines against such pathogens and tumors.

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117 citations in Web of Science
113 citations in Scopus

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Collaboration types
Domestic collaboration
Web of Science research areas
Immunology
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