tetano
Editor, Senior Moderator
Oncotarget. 2016 Jun 14. doi: 10.18632/oncotarget.10047. [Epub ahead of print]
[h=1]IL-2 and IL-6 cooperate to enhance the generation of influenza-specific CD8 T cells responding to live influenza virus in aged mice and humans.[/h] Zhou X[SUP]1[/SUP], Hopkins JW[SUP]1[/SUP], Wang C[SUP]1[/SUP], Brahmakshatriya V[SUP]2[/SUP], Swain SL[SUP]2[/SUP], Kuchel GA[SUP]1[/SUP], Haynes L[SUP]1[/SUP], McElhaney JE[SUP]1,[/SUP][SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] An age-related decline in cytolytic activity has been described in CD8+ T cells and we have previously shown that the poor CD8+ effector T cell responses to influenza A/H3N2 challenge result from a decline in the proportion and function of these cytolytic T lymphocytes (CTL). Here, we describe that addition of exogenous cytokines to influenza-stimulated PBMC from both aged mice and humans, enhances the generation of influenza specific CD8 CTL by increasing their proliferation and survival. Our data show that the addition of IL-2 and IL-6 to splenocytes from mice previously infected with influenza virus restores the aged CD8+ T cell response to that observed in young mice. In humans, IL-2 plus IL-6 also reduces the proportion of apoptotic effector CD8+ T cells to levels resembling those of younger adults. In HLA-A2+ donors, MHC Class I tetramer staining showed that adding both exogenous IL-2 and IL-6 resulted in greater differentiation into influenza-specific effector CD8+ T cells. Since this effect of IL-2/IL-6 supplementation can be reproduced with the addition of Toll-like receptor agonists, it may be possible to exploit this mechanism and design new vaccines to improve the CD8 T cell response to influenza vaccination in older adults.
[h=4]KEYWORDS:[/h] CD8 T cell; Gerotarget; aging; granzyme B; influenza; interleukin-2; interleukin-6; perforin
PMID: 27322555 [PubMed - as supplied by publisher] Free full text
[h=1]IL-2 and IL-6 cooperate to enhance the generation of influenza-specific CD8 T cells responding to live influenza virus in aged mice and humans.[/h] Zhou X[SUP]1[/SUP], Hopkins JW[SUP]1[/SUP], Wang C[SUP]1[/SUP], Brahmakshatriya V[SUP]2[/SUP], Swain SL[SUP]2[/SUP], Kuchel GA[SUP]1[/SUP], Haynes L[SUP]1[/SUP], McElhaney JE[SUP]1,[/SUP][SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] An age-related decline in cytolytic activity has been described in CD8+ T cells and we have previously shown that the poor CD8+ effector T cell responses to influenza A/H3N2 challenge result from a decline in the proportion and function of these cytolytic T lymphocytes (CTL). Here, we describe that addition of exogenous cytokines to influenza-stimulated PBMC from both aged mice and humans, enhances the generation of influenza specific CD8 CTL by increasing their proliferation and survival. Our data show that the addition of IL-2 and IL-6 to splenocytes from mice previously infected with influenza virus restores the aged CD8+ T cell response to that observed in young mice. In humans, IL-2 plus IL-6 also reduces the proportion of apoptotic effector CD8+ T cells to levels resembling those of younger adults. In HLA-A2+ donors, MHC Class I tetramer staining showed that adding both exogenous IL-2 and IL-6 resulted in greater differentiation into influenza-specific effector CD8+ T cells. Since this effect of IL-2/IL-6 supplementation can be reproduced with the addition of Toll-like receptor agonists, it may be possible to exploit this mechanism and design new vaccines to improve the CD8 T cell response to influenza vaccination in older adults.
[h=4]KEYWORDS:[/h] CD8 T cell; Gerotarget; aging; granzyme B; influenza; interleukin-2; interleukin-6; perforin
PMID: 27322555 [PubMed - as supplied by publisher] Free full text