Nature, 2006
1.?PD-1 is upregulated during chronic viral infection
acute/chronic infections in adult mice: LCMV different strain
2.?PD-L1 blockade enhances viral control and T-cell responses
LCMV clone-13-infected mice were treated with anti-PD-L1 from day 23 to day 37 post-infection
Test:
A.?Virus-specific CD8 T-cell numbers in the spleen
B.?Cytokine production(IFN、TNF)by splenocytes after stimulation
C.? Viral titers in the tissues
PD-L1 blockade did not increase virus-specific CD8 T-cell responses in the acute infection model (data not shown).
3.?Restoring function in ‘helpless’ CD8 T cells
whether blockade of the PD-1/PD-L1 inhibitory pathway would enhance CD8 T-cell responses in the absence of CD4 T cell help？
Mice were depleted of CD4 T cells and then infected with LCMV clone 13. After at least 40 days, chronically infected mice were treated with anti-PD-L1 for two weeks.
Test:
A.?Virus-specific CD8 T-cell numbers in the spleen and other tissues
B.?Cytokine production (IFN) by splenocytes after stimulation
C.?Viral titers in the tissues
D.?BrdU incorporation and Ki67 expression: 變多的T細(xì)胞是否是增殖而來敦锌？
E.?Direct ex vivo 51Cr-release activity using target cells coated with epitopes：CTL的裂解能力？
F.?degranulation by LCMV-specific CD8 T cells：CTL的裂解能力污尉？
Treatment of chronically infected mice with anti-CTLA-4 blocking antibody had no effect on either virus-specific T-cell responses or viral control.
4.?Proliferation of exhausted CD8 T cells
whether?exhausted CD8 T cells self-renew or proliferate from naive T cells? 變多的CD8 T cell從何而來？
發(fā)現(xiàn)donor exhausted CD8+ T cell的數(shù)量變多往产，說明PD-1可以使exhausted的細(xì)胞增殖被碗，但不排除可能存在naive T cell對(duì)增殖的貢獻(xiàn)，所以進(jìn)一步分選PD-1+ CD8 T cell仿村，如下：
Expanded population of virus specific CD8 T cells does not suddenly decline after the antibody treatment has been stopped.
5.?Infection of PD-L1-/- mice
PD-1 KO mice
