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 language | English (US) |
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Pages (from-to) | 947-955 |
Number of pages | 9 |
Journal | Journal of Experimental Medicine |
Volume | 198 |
Issue number | 6 |
DOIs | |
State | Published - Sep 15 2003 |
Externally published | Yes |
Keywords
- CD28
- CD8 T cells
- Costimulation
- Interleukin-2
- Memory response
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology