TY - JOUR
T1 - Loss of IL-7R and IL-15R expression is associated with disappearance of memory T cells in respiratory tract following influenza infection
AU - Shen, Ching Hung
AU - Ge, Qing
AU - Talay, Oezcan
AU - Eisen, Herman N.
AU - García-Sastre, Adolfo
AU - Chen, Jianzhu
PY - 2008/1/1
Y1 - 2008/1/1
N2 - Following influenza virus infection, memory CD8 T cells are found in both lymphoid and nonlymphoid organs, where they exhibit striking differences in survival. We have assessed persistence, phenotype, and function of memory CD8 T cells expressing the same TCR in the airways, lung parenchyma, and spleen following influenza virus infection in mice. In contrast to memory CD8 T cells in the spleen, those residing in the airways gradually lost expression of IL-7R and IL-15R, did not respond to IL-7 and/or IL-15, and exhibited poor survival both in vivo and in vitro. Following adoptive transfer into the airways, splenic memory CD8 T cells also down-regulated IL-7R and IL-15R expression and failed to undergo homeostatic proliferation. Thus, although cytokines IL-7 and IL-15 play an essential role in memory CD8 T cell homeostasis in lymphoid organs, the levels of IL-7R and IL-15R expression likely set a threshold for the homeostatic regulation of memory CD8 T cells in the airways. These findings provide a molecular explanation for the gradual loss of airway memory CD8 T cells and heterosubtypic immunity following influenza infection.
AB - Following influenza virus infection, memory CD8 T cells are found in both lymphoid and nonlymphoid organs, where they exhibit striking differences in survival. We have assessed persistence, phenotype, and function of memory CD8 T cells expressing the same TCR in the airways, lung parenchyma, and spleen following influenza virus infection in mice. In contrast to memory CD8 T cells in the spleen, those residing in the airways gradually lost expression of IL-7R and IL-15R, did not respond to IL-7 and/or IL-15, and exhibited poor survival both in vivo and in vitro. Following adoptive transfer into the airways, splenic memory CD8 T cells also down-regulated IL-7R and IL-15R expression and failed to undergo homeostatic proliferation. Thus, although cytokines IL-7 and IL-15 play an essential role in memory CD8 T cell homeostasis in lymphoid organs, the levels of IL-7R and IL-15R expression likely set a threshold for the homeostatic regulation of memory CD8 T cells in the airways. These findings provide a molecular explanation for the gradual loss of airway memory CD8 T cells and heterosubtypic immunity following influenza infection.
UR - http://www.scopus.com/inward/record.url?scp=40449112705&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.180.1.171
DO - 10.4049/jimmunol.180.1.171
M3 - Article
C2 - 18097017
AN - SCOPUS:40449112705
SN - 0022-1767
VL - 180
SP - 171
EP - 178
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -