tetano
Editor, Senior Moderator
J Immunol. 2018 Oct 26. pii: ji1701672. doi: 10.4049/jimmunol.1701672. [Epub ahead of print]
[h=1]Limited Phenotypic and Functional Plasticity of Influenza Virus-Specific Memory CD8[SUP]+[/SUP] T Cells during Activation in an Alternative Cytokine Environment.[/h] Harland KL[SUP]1[/SUP], Fox A[SUP]1[/SUP], N?ssing S[SUP]1[/SUP], Hensen L[SUP]1[/SUP], Kedzierska K[SUP]1[/SUP], Turner SJ[SUP]1[/SUP], Kelso A[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Naive CD8[SUP]+[/SUP] T cells show phenotypic, functional, and epigenetic plasticity, enabling differentiation into distinct cellular states. However, whether memory CD8[SUP]+[/SUP] T cells demonstrate similar flexibility upon recall is poorly understood. We investigated the potential of influenza A virus (IAV)-specific memory CD8[SUP]+[/SUP] T cells from mice to alter their phenotype and function in response to reactivation in the presence of IL-4 and anti-IFN-γ Ab (type 2 conditions). Compared with naive CD8[SUP]+[/SUP] T cells, only a small proportion of IAV-specific memory T cells exhibited phenotypic and functional plasticity after clonal activation under type 2 conditions. The potential for modulation of cell-surface phenotype (CD8α expression) was associated with specific epigenetic changes at the Cd8a locus, was greater in central memory T cells than effector memory T cells, and was observed in endogenous memory cells of two TCR specificities. Using a novel technique for intracellular cytokine staining of small clonal populations, we showed that IAV-specific memory CD8[SUP]+[/SUP] T cells reactivated under type 2 conditions displayed robust IFN-γ expression and, unlike naive CD8[SUP]+[/SUP] T cells activated under type 2 conditions, produced little IL-4 protein. Secondary activation of memory cells under type 2 conditions increased GATA-3 levels with minimal change in T-bet levels. These data suggest that a small population of memory cells, especially central memory T cells, exhibits plasticity; however, most IAV-specific memory CD8[SUP]+[/SUP] T cells resist reprogramming upon reactivation and retain the functional state established during priming.
PMID: 30366957 DOI: 10.4049/jimmunol.1701672
[h=1]Limited Phenotypic and Functional Plasticity of Influenza Virus-Specific Memory CD8[SUP]+[/SUP] T Cells during Activation in an Alternative Cytokine Environment.[/h] Harland KL[SUP]1[/SUP], Fox A[SUP]1[/SUP], N?ssing S[SUP]1[/SUP], Hensen L[SUP]1[/SUP], Kedzierska K[SUP]1[/SUP], Turner SJ[SUP]1[/SUP], Kelso A[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Naive CD8[SUP]+[/SUP] T cells show phenotypic, functional, and epigenetic plasticity, enabling differentiation into distinct cellular states. However, whether memory CD8[SUP]+[/SUP] T cells demonstrate similar flexibility upon recall is poorly understood. We investigated the potential of influenza A virus (IAV)-specific memory CD8[SUP]+[/SUP] T cells from mice to alter their phenotype and function in response to reactivation in the presence of IL-4 and anti-IFN-γ Ab (type 2 conditions). Compared with naive CD8[SUP]+[/SUP] T cells, only a small proportion of IAV-specific memory T cells exhibited phenotypic and functional plasticity after clonal activation under type 2 conditions. The potential for modulation of cell-surface phenotype (CD8α expression) was associated with specific epigenetic changes at the Cd8a locus, was greater in central memory T cells than effector memory T cells, and was observed in endogenous memory cells of two TCR specificities. Using a novel technique for intracellular cytokine staining of small clonal populations, we showed that IAV-specific memory CD8[SUP]+[/SUP] T cells reactivated under type 2 conditions displayed robust IFN-γ expression and, unlike naive CD8[SUP]+[/SUP] T cells activated under type 2 conditions, produced little IL-4 protein. Secondary activation of memory cells under type 2 conditions increased GATA-3 levels with minimal change in T-bet levels. These data suggest that a small population of memory cells, especially central memory T cells, exhibits plasticity; however, most IAV-specific memory CD8[SUP]+[/SUP] T cells resist reprogramming upon reactivation and retain the functional state established during priming.
PMID: 30366957 DOI: 10.4049/jimmunol.1701672