[Association of PD-1 expression on CD4+ CD25 nt/hi CD127 lo regulatory T cells with disease progression in HIV-1 infected patients].
OBJECTIVE
To investigate whether Programmed death-1 (PD-1) expression on peripheral CD4(+)CD25(nt/hi)CD127(lo) regulatory T cells (Treg) was associated with disease progression in HIV-1-infected patients.


METHODS
Peripheral blood from 108 HIV-1-infected patients in distinct disease progression statuses and 27 healthy individuals were collected in the present investigation. PBMCs were isolated by centrifugation on Ficoll-Hypaque, followed by staining with anti-CD4-PerCP, anti-CD25-FITC, anti-CD127-PE and anti-PD-1-APC. PD-1 expression on Treg was analyzed by four-color staining flow cytometry. CD4(+) T cell absolute counts were determined using Multitest CD3/CD4/CD8/CD45 kit and plasma viral loads were detected on NucliSens EasyQ. All data were analyzed using SPSS14.0 software.


RESULTS
In peripheral blood of healthy individuals, Treg expressed PD-1 at very low levels (1.72%+/-0.65%). In contrast, Treg from HIV-1-infected patients showed a significantly increased PD-1 expression (5.33%+/-2.24%, P<0.01). Moreover, AIDS patients exhibited statistically higher PD-1 expression on Treg (7.87%+/-2.23%) than newly HIV-1 infected patients (3.22%+/-1.01%, P<0.05) and patients in progression to AIDS(5.21%+/-1.72%, P<0.05). PD-1 up-regulation on Treg was closely correlated with reduced CD4(+) T cell absolute counts but elevated plasma viral load.


CONCLUSIONS
Overall, we found that PD-1 expression on peripheral Treg was up-regulated and correlated with disease progression in HIV-1-infected patients for the first time. These findings not only extend our understanding of how Treg functions in HIV-1-infected patients but also support the notion that blocking PD-1/PD-L1 interactions may represent a potential therapeutic strategy for HIV-1-infected patients.
Cao
Qing-hua
QH
AIDS/STD Department, Shanghai Municipal Center for Disease Control & Prevention/Shanghai Municipal Institute of Preventive Medicine, Shanghai 200336, China.
Xue
Yi-le
YL
Wang
Ying
Y
D000328:Adult; D000368:Aged; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation; D055815:Young Adult
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor