TY - JOUR
T1 - Protective Capacity of Memory CD8+ T Cells Is Dictated by Antigen Exposure History and Nature of the Infection
AU - Nolz, Jeffrey C.
AU - Harty, John T.
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health (AI42767, AI46653, AI50073, and AI59752; J.T.H.) and a Career Development Award from The Leukemia and Lymphoma Society (J.C.N.). The authors would like to thank members of the Harty Lab for helpful discussions and V. Badovinac, S. Perlman, and S. Varga for critical review of the manuscript. We thank S. Perlman and J. Netland for reagents and technical assistance with MHV and L. Epping, L. Hancox and J. Hoang for technical assistance. J.C.N. designed and performed experiments, analyzed data, and wrote the paper. J.T.H. designed experiments, analyzed data, and wrote the paper.
PY - 2011/5/27
Y1 - 2011/5/27
N2 - Infection or vaccination confers heightened resistance to pathogen rechallenge because of quantitative and qualitative differences between naive and primary memory T cells. Herein, we show that secondary (boosted) memory CD8+ T cells were better than primary memory CD8+ T cells in controlling some, but not all acute infections with diverse pathogens. However, secondary memory CD8+ T cells were less efficient than an equal number of primary memory cells at preventing chronic LCMV infection and are more susceptible to functional exhaustion. Importantly, localization of memory CD8+ T cells within lymph nodes, which is reduced by antigen restimulation, was critical for both viral control in lymph nodes and for the sustained CD8+ T cell response required to prevent chronic LCMV infection. Thus, repeated antigen stimulation shapes memory CD8+ T cell populations to either enhance or decrease per cell protective immunity in a pathogen-specific manner, a concept of importance in vaccine design against specific diseases.
AB - Infection or vaccination confers heightened resistance to pathogen rechallenge because of quantitative and qualitative differences between naive and primary memory T cells. Herein, we show that secondary (boosted) memory CD8+ T cells were better than primary memory CD8+ T cells in controlling some, but not all acute infections with diverse pathogens. However, secondary memory CD8+ T cells were less efficient than an equal number of primary memory cells at preventing chronic LCMV infection and are more susceptible to functional exhaustion. Importantly, localization of memory CD8+ T cells within lymph nodes, which is reduced by antigen restimulation, was critical for both viral control in lymph nodes and for the sustained CD8+ T cell response required to prevent chronic LCMV infection. Thus, repeated antigen stimulation shapes memory CD8+ T cell populations to either enhance or decrease per cell protective immunity in a pathogen-specific manner, a concept of importance in vaccine design against specific diseases.
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U2 - 10.1016/j.immuni.2011.03.020
DO - 10.1016/j.immuni.2011.03.020
M3 - Article
C2 - 21549619
AN - SCOPUS:79956320655
SN - 1074-7613
VL - 34
SP - 781
EP - 793
JO - Immunity
JF - Immunity
IS - 5
ER -