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Dendritic cells and CD28 costimulation are required to sustain virus-specific CD8+ T cell responses during the effector phase in vivo
Journal article   Open access   Peer reviewed

Dendritic cells and CD28 costimulation are required to sustain virus-specific CD8+ T cell responses during the effector phase in vivo

Douglas V Dolfi, Priyanka A Duttagupta, Alina C Boesteanu, Yvonne M Mueller, Caspian H Oliai, Annie B Borowski and Peter D Katsikis
The Journal of immunology (1950), v 186(8), pp 4599-4608
15 Apr 2011
DOI: https://doi.org/10.4049/jimmunol.1001972
PMID: 21389258
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://www.jimmunol.org/content/jimmunol/186/8/4599.full.pdfView
Published, Version of Record (VoR) Open
url
https://doi.org/10.4049/jimmunol.1001972View
Published, Version of Record (VoR) Open

Abstract

Abridged Index Medicus
Although much is known about the initiation of immune responses, much less is known about what controls the effector phase. CD8(+) T cell responses are believed to be programmed in lymph nodes during priming without any further contribution by dendritic cells (DCs) and Ag. In this study, we report the requirement for DCs, Ag, and CD28 costimulation during the effector phase of the CD8(+) T cell response. Depleting DCs or blocking CD28 after day 6 of primary influenza A virus infection decreases the virus-specific CD8(+) T cell response by inducing apoptosis, and this results in decreased viral clearance. Furthermore, effector CD8(+) T cells adoptively transferred during the effector phase fail to expand without DC, CD28 costimulation, and cognate Ag. The absence of costimulation also leads to reduced survival of virus-specific effector cells as they undergo apoptosis mediated by the proapoptotic molecule Bim. Finally, IL-2 treatment restored the effector response in the absence of CD28 costimulation. Thus, in contrast to naive CD8(+) T cells, which undergo an initial Ag-independent proliferation, effector CD8(+) T cells expanding in the lungs during the effector phase require Ag, CD28 costimulation, and DCs for survival and expansion. These requirements would greatly impair effector responses against viruses and tumors that are known to inhibit DC maturation and in chronic infections and aging where CD28(-/-) CD8(+) T cells accumulate.

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