TY - JOUR
T1 - Viral antigen and extensive division maintain virus-specific CD8 T cells during chronic infection
AU - Shin, Haina
AU - Blackburn, Shawn D.
AU - Blattman, Joseph N.
AU - Wherry, E. John
PY - 2007/4/16
Y1 - 2007/4/16
N2 - Efficient maintenance of memory CD8 T cells is central to long-term protective immunity. IL-7- and IL-15-driven homeostatic proliferation is essential for long-term memory CD8 T cell persistence after acute infections. During chronic infections, however, virus-specific CD8 T cells respond poorly to these cytokines. Yet, virus-specific CD8 T cells often persist for long periods of time during chronic infections. We have addressed this apparent paradox by examining the mechanism for maintaining virus-specific CD8 T cells during chronic infection. We find that homeostatic cytokines (e.g., IL-7/15), inflammatory signals, and priming of recent thymic emigrants are not sufficient to maintain virus-specific CD8 T cells over time during chronic infection. Rather, our results demonstrate that viral peptide is required for virus-specific CD8 T cell persistence during chronic infection. Moreover, this viral antigen-dependent maintenance results in a dramatically different type of T cell division than is normally observed during memory T cell homeostasis. Rather than undergoing slow, steady homeostatic turnover during chronic viral infection, CD8 T cells undergo extensive peptide-dependent division, yet cell numbers remain relatively stable. These results indicate that antigen-specific CD8 T cell responses during persisting infection are maintained by a mechanism distinct from that after acute infection. JEM
AB - Efficient maintenance of memory CD8 T cells is central to long-term protective immunity. IL-7- and IL-15-driven homeostatic proliferation is essential for long-term memory CD8 T cell persistence after acute infections. During chronic infections, however, virus-specific CD8 T cells respond poorly to these cytokines. Yet, virus-specific CD8 T cells often persist for long periods of time during chronic infections. We have addressed this apparent paradox by examining the mechanism for maintaining virus-specific CD8 T cells during chronic infection. We find that homeostatic cytokines (e.g., IL-7/15), inflammatory signals, and priming of recent thymic emigrants are not sufficient to maintain virus-specific CD8 T cells over time during chronic infection. Rather, our results demonstrate that viral peptide is required for virus-specific CD8 T cell persistence during chronic infection. Moreover, this viral antigen-dependent maintenance results in a dramatically different type of T cell division than is normally observed during memory T cell homeostasis. Rather than undergoing slow, steady homeostatic turnover during chronic viral infection, CD8 T cells undergo extensive peptide-dependent division, yet cell numbers remain relatively stable. These results indicate that antigen-specific CD8 T cell responses during persisting infection are maintained by a mechanism distinct from that after acute infection. JEM
UR - http://www.scopus.com/inward/record.url?scp=34247328511&partnerID=8YFLogxK
U2 - 10.1084/jem.20061937
DO - 10.1084/jem.20061937
M3 - Article
C2 - 17420267
AN - SCOPUS:34247328511
SN - 0022-1007
VL - 204
SP - 941
EP - 949
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 4
ER -