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Restoration of CD28 Expression in CD28(−) CD8(+) Memory Effector T Cells Reconstitutes Antigen-induced IL-2 Production

The control of many persistent viral infections by Ag-specific cytolytic CD8(+) T cells requires a concurrent virus-specific CD4(+) Th cell response. This reflects in part a requirement of activated effector CD8(+) T cells for paracrine IL-2 production as a growth and survival factor. In human CMV a...

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Detalles Bibliográficos
Autores principales: Topp, Max S., Riddell, Stanley R., Akatsuka, Yoshiki, Jensen, Michael C., Blattman, Joseph N., Greenberg, Philip D.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194206/
https://www.ncbi.nlm.nih.gov/pubmed/12963692
http://dx.doi.org/10.1084/jem.20021288
Descripción
Sumario:The control of many persistent viral infections by Ag-specific cytolytic CD8(+) T cells requires a concurrent virus-specific CD4(+) Th cell response. This reflects in part a requirement of activated effector CD8(+) T cells for paracrine IL-2 production as a growth and survival factor. In human CMV and HIV infection, the majority of differentiated virus-specific CD8(+) T cells notably lose the ability to produce IL-2 but also lose expression of CD28, a costimulatory molecule. Analysis of the fraction of memory CD8(+) T cells that continue to express CD28 revealed these cells retain the ability to produce IL-2. Therefore, we examined if IL-2 production by CD28(−) CD8(+) T cells could be restored by introduction of a constitutively expressed CD28 gene. Expression of CD28 in CD28(−) CD8(+) CMV- and HIV-specific CD8(+) T cells reconstituted the ability to produce IL-2, which could sustain an autocrine proliferative response after Ag recognition. These results suggest that the loss of CD28 expression during differentiation of memory/effector CD8(+) T cells represents a decisive step in establishing regulation of responding CD8(+) T cells, increasing the dependence on CD4(+) Th for proliferation after target recognition, and has implications for the treatment of viral disease with adoptively transferred CD8(+) T cells.