Abstract
Naive CD8+ T cells show phenotypic, functional, and epigenetic plasticity, enabling differentiation into distinct cellular states. However, whether memory CD8+ T cells demonstrate similar flexibility upon recall is poorly understood. We investigated the potential of influenza A virus (IAV)-specific memory CD8+ 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+ 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+ T cells reactivated under type 2 conditions displayed robust IFN-γ expression and, unlike naive CD8+ 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+ T cells resist reprogramming upon reactivation and retain the functional state established during priming.
| Original language | English |
|---|---|
| Pages (from-to) | 3282-3293 |
| Number of pages | 12 |
| Journal | Journal of Immunology |
| Volume | 201 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 1 Dec 2018 |
Cite this
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Limited Phenotypic and Functional Plasticity of Influenza Virus-Specific Memory CD8+ T Cells during Activation in an Alternative Cytokine Environment. / Harland, Kim L.; Fox, Annette; Nüssing, Simone; Hensen, Luca; Kedzierska, Katherine; Turner, Stephen J.; Kelso, Anne.
In: Journal of Immunology, Vol. 201, No. 11, 01.12.2018, p. 3282-3293.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Limited Phenotypic and Functional Plasticity of Influenza Virus-Specific Memory CD8+ T Cells during Activation in an Alternative Cytokine Environment
AU - Harland, Kim L.
AU - Fox, Annette
AU - Nüssing, Simone
AU - Hensen, Luca
AU - Kedzierska, Katherine
AU - Turner, Stephen J.
AU - Kelso, Anne
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Naive CD8+ T cells show phenotypic, functional, and epigenetic plasticity, enabling differentiation into distinct cellular states. However, whether memory CD8+ T cells demonstrate similar flexibility upon recall is poorly understood. We investigated the potential of influenza A virus (IAV)-specific memory CD8+ 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+ 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+ T cells reactivated under type 2 conditions displayed robust IFN-γ expression and, unlike naive CD8+ 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+ T cells resist reprogramming upon reactivation and retain the functional state established during priming.
AB - Naive CD8+ T cells show phenotypic, functional, and epigenetic plasticity, enabling differentiation into distinct cellular states. However, whether memory CD8+ T cells demonstrate similar flexibility upon recall is poorly understood. We investigated the potential of influenza A virus (IAV)-specific memory CD8+ 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+ 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+ T cells reactivated under type 2 conditions displayed robust IFN-γ expression and, unlike naive CD8+ 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+ T cells resist reprogramming upon reactivation and retain the functional state established during priming.
UR - http://www.scopus.com/inward/record.url?scp=85056693929&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1701672
DO - 10.4049/jimmunol.1701672
M3 - Article
VL - 201
SP - 3282
EP - 3293
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 11
ER -