TY - JOUR
T1 - The longevity of memory CD8 T cell responses after repetitive antigen stimulations
AU - Rai, Deepa
AU - Martin, Matthew D.
AU - Badovinac, Vladimir P.
PY - 2014/6/15
Y1 - 2014/6/15
N2 - In experimental models in which the Ag-stimulation history of memory CD8 T cell populations was clearly defined (adoptive transfer of a known number of TCR-transgenic memory CD8 T cells), all facets of the ensuing CD8 T cell responses, including proliferative expansion, duration and extent of contraction, diversification of memory CD8 T cell transcriptomes, and life-long survival, were dependent on the number of prior Ag encounters. However, the extent to which sequential adoptive-transfer models reflect the physiological scenario in which memory CD8 T cells are generated by repetitive Ag challenges of individual hosts (no adoptive transfer involved) is not known. Direct comparison of endogenous memory CD8 T cell responses generated in repetitively infected hosts revealed that recurrent homologous boosting was required to preserve the numbers and increase the phenotypic and functional complexity of the developing memory CD8 T cell pool. Although life-long survival of the memory CD8 T cells was not impacted, phenotype (i.e., upregulation of CD62L) and function (i.e., homeostatic turnover, Ag-stimulated IL-2 production) of repeatedly stimulated memory CD8 T cells were dependent on time after last Ag encounter. Therefore, repetitive Ag challenges of individual hosts can substantially influence the numerical and functional attributes of polyclonal memory CD8 T cells, a notion with important implications for the design of future vaccination strategies aimed at increasing the number of protective memory CD8 T cells.
AB - In experimental models in which the Ag-stimulation history of memory CD8 T cell populations was clearly defined (adoptive transfer of a known number of TCR-transgenic memory CD8 T cells), all facets of the ensuing CD8 T cell responses, including proliferative expansion, duration and extent of contraction, diversification of memory CD8 T cell transcriptomes, and life-long survival, were dependent on the number of prior Ag encounters. However, the extent to which sequential adoptive-transfer models reflect the physiological scenario in which memory CD8 T cells are generated by repetitive Ag challenges of individual hosts (no adoptive transfer involved) is not known. Direct comparison of endogenous memory CD8 T cell responses generated in repetitively infected hosts revealed that recurrent homologous boosting was required to preserve the numbers and increase the phenotypic and functional complexity of the developing memory CD8 T cell pool. Although life-long survival of the memory CD8 T cells was not impacted, phenotype (i.e., upregulation of CD62L) and function (i.e., homeostatic turnover, Ag-stimulated IL-2 production) of repeatedly stimulated memory CD8 T cells were dependent on time after last Ag encounter. Therefore, repetitive Ag challenges of individual hosts can substantially influence the numerical and functional attributes of polyclonal memory CD8 T cells, a notion with important implications for the design of future vaccination strategies aimed at increasing the number of protective memory CD8 T cells.
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U2 - 10.4049/jimmunol.1301063
DO - 10.4049/jimmunol.1301063
M3 - Article
C2 - 24829415
AN - SCOPUS:84902126799
SN - 0022-1767
VL - 192
SP - 5652
EP - 5659
JO - Journal of Immunology
JF - Journal of Immunology
IS - 12
ER -