Loss of IL-7R and IL-15R expression is associated with disappearance of memory T cells in respiratory tract following influenza infection.
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.
Shen
Ching-Hung
CH
Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Ge
Qing
Q
Talay
Oezcan
O
Eisen
Herman N
HN
García-Sastre
Adolfo
A
Chen
Jianzhu
J
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015536:Down-Regulation; D006801:Humans; D007156:Immunologic Memory; D007251:Influenza, Human / Q000276:immunology*; D019409:Interleukin-15 / Q000235:genetics / Q000378:metabolism; D015851:Interleukin-7 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D053647:Receptors, Interleukin-15 / Q000172:deficiency*; D020395:Receptors, Interleukin-7 / Q000172:deficiency*; D013154:Spleen / Q000276:immunology / Q000821:virology
D019409:Interleukin-15; D015851:Interleukin-7; D053647:Receptors, Interleukin-15; D020395:Receptors, Interleukin-7