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Restoring function in exhausted CD8 T cells during chronic viral infection
TLDR
It is found that even in persistently infected mice that were lacking CD4 T-cell help, blockade of the PD-1/PD-L1 inhibitory pathway had a beneficial effect on the ‘helpless’ CD8 T cells, restoring their ability to undergo proliferation, secrete cytokines, kill infected cells and decrease viral load.
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Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells
TLDR
Increased expression of the interleukin 7 receptor α-chain (IL-7Rα) identifies the effector CD8 T cells that will differentiate into memory cells, and this marker may be useful in predicting the number of memory T cells generated after infection or immunization.
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Molecular signature of CD8+ T cell exhaustion during chronic viral infection.
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Lineage relationship and protective immunity of memory CD8 T cell subsets
TLDR
It is proposed that TCM and TEM do not necessarily represent distinct subsets, but are part of a continuum in a linear naive → effector → TEM → TCM differentiation pathway.
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Viral Persistence Alters CD8 T-Cell Immunodominance and Tissue Distribution and Results in Distinct Stages of Functional Impairment
TLDR
A model is proposed in which antigen levels drive the hierarchical loss of different CD8 T-cell effector functions during chronic infection, leading to distinct stages of functional impairment and eventually to physical deletion of virus-specific T cells.
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PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression
TLDR
The data indicate that the immunoregulatory PD-1/PD-L1 pathway is operative during a persistent viral infection in humans, and define a reversible defect in HIV-specific T-cell function.
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Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection.
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Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin
TLDR
These key transcription factors T-bet and eomesodermin link the long-term renewal of memory CD8+ T cells to their characteristic effector potency, and are responsible for inducing enhanced expression of CD122, the receptor specifying interleukin 15 responsiveness.
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mTOR regulates memory CD8 T cell differentiation
TLDR
It is shown that mTOR (mammalian target of rapamycin, also known as FRAP1) is a major regulator of memory CD8 T-cell differentiation, and in contrast to what was expected, the immunosuppressive drug Rapamycin has immunostimulatory effects on the generation of memoryCD8 T cells.
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Viral Immune Evasion Due to Persistence of Activated T Cells Without Effector Function
TLDR
The persistence of activated virus-specific CD8 T cells without effector function reveals a novel mechanism for silencing antiviral immune responses and also offers new possibilities for enhancingCD8 T cell immunity in chronically infected hosts.
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