Restoration of CD28 expression in CD28- CD8+ memory effector T cells reconstitutes antigen-induced IL-2 production

Max S. Topp, Stanley R. Riddell, Yoshiki Akatsuka, Michael C. Jensen, Joseph N. Blattman, Philip D. Greenberg

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117 Citations (Scopus)


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 celts 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 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.

Original languageEnglish
Pages (from-to)947-955
Number of pages9
JournalJournal of Experimental Medicine
Issue number6
Publication statusPublished - 15-09-2003

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Topp, M. S., Riddell, S. R., Akatsuka, Y., Jensen, M. C., Blattman, J. N., & Greenberg, P. D. (2003). Restoration of CD28 expression in CD28- CD8+ memory effector T cells reconstitutes antigen-induced IL-2 production. Journal of Experimental Medicine, 198(6), 947-955.