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

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 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.

• Authors: Max S Topp, Stanley R Riddell, Yoshiki Akatsuka, Michael C Jensen, Joseph N Blattman, Philip D Greenberg
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 198 Issue 6 Pg. 947-55 (Sep 15 2003) ISSN: 0022-1007 [Print] United States
• PMID: 12963692 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• CD28 Antigens
• HLA-A Antigens
• HLA-A*02:01 antigen
• HLA-A2 Antigen
• Interleukin-2

Topics

• CD28 Antigens (metabolism)
• Cytomegalovirus (immunology)
• Cytotoxicity, Immunologic
• HIV-1 (immunology)
• HLA-A Antigens (metabolism)
• HLA-A2 Antigen
• Humans
• Immunologic Memory
• Interleukin-2 (metabolism)
• Lymphocyte Activation
• T-Lymphocyte Subsets (immunology, metabolism)
• T-Lymphocytes, Regulatory (immunology, metabolism)