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Dynamics of influenza-induced lung-resident memory T cells underlie waning heterosubtypic immunity

tetano

Editor, Senior Moderator
Sci Immunol. 2017 Jan 6;2(7). pii: eaag2031. doi: 10.1126/sciimmunol.aag2031. Epub 2017 Jan 6.
[h=1]Dynamics of influenza-induced lung-resident memory T cells underlie waning heterosubtypic immunity.[/h] Sl?tter B[SUP]1,[/SUP][SUP]2[/SUP], Van Braeckel-Budimir N[SUP]1[/SUP], Abboud G[SUP]3[/SUP], Varga SM[SUP]1,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Salek-Ardakani S[SUP]3[/SUP], Harty JT[SUP]6,[/SUP][SUP]4,[/SUP][SUP]5[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] Lung-resident memory CD8 T cells (T[SUB]RM[/SUB]) induced by influenza A virus (IAV) that are pivotal for providing subtype-transcending protection against IAV infection (heterosubtypic immunity) are not maintained long term, causing gradual loss of protection. The short-lived nature of lung T[SUB]RM[/SUB] contrasts sharply with long-term maintenance of T[SUB]RM[/SUB] induced by localized infections in the skin and in other tissues. We show that the decline in lung T[SUB]RM[/SUB] is determined by an imbalance between apoptosis and lung recruitment and conversion to T[SUB]RM[/SUB] of circulating memory cells. We show that circulating effector memory cells (T[SUB]EM[/SUB]) rather than central memory cells (T[SUB]CM[/SUB]) are the precursors for conversion to lung T[SUB]RM[/SUB] Time-dependent changes in expression of genes critical for lymphocyte trafficking and T[SUB]RM[/SUB] differentiation, in concert with enrichment of T[SUB]CM[/SUB], diminish the capacity of circulating memory CD8 T cells to form T[SUB]RM[/SUB] with time, explaining why IAV-induced T[SUB]RM[/SUB] are not stably maintained. Systemic booster immunization, through increasing the number of circulating T[SUB]EM[/SUB], increases lung T[SUB]RM[/SUB], providing a potential new avenue to enhance IAV vaccines.
Copyright ? 2017, American Association for the Advancement of Science.


PMID: 28783666 DOI: 10.1126/sciimmunol.aag2031
 
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