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

Research output: Contribution to journalArticlepeer-review

117 Scopus citations

Abstract

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 (US)
Pages (from-to)947-955
Number of pages9
JournalJournal of Experimental Medicine
Volume198
Issue number6
DOIs
StatePublished - Sep 15 2003
Externally publishedYes

Keywords

  • CD28
  • CD8 T cells
  • Costimulation
  • Interleukin-2
  • Memory response

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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