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 |
|---|---|
| Pages (from-to) | 947-955 |
| Number of pages | 9 |
| Journal | Journal of Experimental Medicine |
| Volume | 198 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 15-09-2003 |
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All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Immunology
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Restoration of CD28 expression in CD28- CD8+ memory effector T cells reconstitutes antigen-induced IL-2 production. / Topp, Max S.; Riddell, Stanley R.; Akatsuka, Yoshiki; Jensen, Michael C.; Blattman, Joseph N.; Greenberg, Philip D.
In: Journal of Experimental Medicine, Vol. 198, No. 6, 15.09.2003, p. 947-955.Research output: Contribution to journal › Article
TY - JOUR
T1 - Restoration of CD28 expression in CD28- CD8+ memory effector T cells reconstitutes antigen-induced IL-2 production
AU - Topp, Max S.
AU - Riddell, Stanley R.
AU - Akatsuka, Yoshiki
AU - Jensen, Michael C.
AU - Blattman, Joseph N.
AU - Greenberg, Philip D.
PY - 2003/9/15
Y1 - 2003/9/15
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.20021288
DO - 10.1084/jem.20021288
M3 - Article
C2 - 12963692
AN - SCOPUS:0141449956
VL - 198
SP - 947
EP - 955
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 6
ER -