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2010-8-2 22:04:11
在进展性HIV-1病毒感染中,CD4+T淋巴细胞的FOXP3表达上调成为疾病严重程度的一个指标
FOXP3 Expression Is Upregulated in CD4+T Cells in Progressive HIV-1 Infection and Is a Marker of Disease Severity
Melinda S. Suchard,1,2,4* Elizabeth Mayne,1,4 Victoria A. Green,1,3,4Sharon Shalekoff,4 Samantha L. Donninger,4 Wendy S. Stevens,1 Clive M. Gray,4 and Caroline T. Tiemessen4
1Haematology and Molecular Medicine, National Health Laboratory Service and University of the Witwatersrand, Johannesburg, South Africa
2Microbiology, National Health Laboratory Service and University of the Witwatersrand, Johannesburg, South Africa
3Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom
4AIDS Virus Research Unit, National Institute for Communicable Disease, Johannesburg, South Africa
Derya Unutmaz, Editor
New York University, United States of America

* E-mail: thesuchards@telkomsa.net
Conceived and designed the experiments: MSS EM VAG SS SLD WS. Performed the experiments: MSS EM VAG. Analyzed the data: MSS. Contributed reagents/materials/analysis tools: MSS SS SLD CMG CTT. Wrote the paper: MSS. Reviewed manuscript: EM VAG SS WS CMG CTT.

Received April 13, 2010; Accepted June 17, 2010.


Abstract
Background
Understanding the role of different classes of T cells during HIV infection is critical to determining which responses correlate with protective immunity. To date, it is unclear whether alterations in regulatory T cell (Treg) function are contributory to progression of HIV infection.

Methodology
FOXP3 expression was measured by both qRT-PCR and by flow cytometry in HIV-infected individuals and uninfected controls together with expression of CD25, GITR and CTLA-4. Cultured peripheral blood mononuclear cells were stimulated with anti-CD3 and cell proliferation was assessed by CFSE dilution.

Principal Findings
HIV infected individuals had significantly higher frequencies of CD4+FOXP3+ T cells (median of 8.11%; range 1.33%–26.27%) than healthy controls (median 3.72%; range 1.3–7.5%; P=0.002), despite having lower absolute counts of CD4+FOXP3+ T cells. There was a significant positive correlation between the frequency of CD4+FOXP3+ T cells and viral load (rho=0.593 P=0.003) and a significant negative correlation with CD4 count (rho=−0.423 P=0.044). 48% of our patients had CD4 counts below 200 cells/µl and these patients showed a marked elevation of FOXP3 percentage (median 10% range 4.07%–26.27%). Assessing the mechanism of increased FOXP3 frequency, we found that the high FOXP3 levels noted in HIV infected individuals dropped rapidly in unstimulated culture conditions but could be restimulated by T cell receptor stimulation. This suggests that the high FOXP3 expression in HIV infected patients is likely due to FOXP3 upregulation by individual CD4+ T cells following antigenic or other stimulation.

Conclusions/Significance
FOXP3 expression in the CD4+ T cell population is a marker of severity of HIV infection and a potential prognostic marker of disease progression.

全文链接:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2909259/?tool=pubmed


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