Restoration of the CD4 T cell compartment after long-term highly active Antiretroviral therapy without phenotypical signs of accelerated immunological aging

被引:55
作者
Vrisekoop, Nienke [1 ,2 ]
van Gent, Rogier [1 ,2 ]
de Boer, Anne Bregje [1 ,2 ]
Otto, Sigrid A. [1 ,2 ]
Borleffs, Jan C. C. [3 ]
Stemgrover, Radjin [4 ,5 ]
Prins, Jan M. [4 ]
Kuijpers, Taco W. [6 ]
Wolfs, Tom F. W. [7 ]
Geelen, Sibyl P. M. [7 ]
Vulto, Irma [2 ,8 ]
Lansdorp, Peter [8 ]
Tesselaar, Kiki [1 ,2 ]
Borghans, Jose A. M. [1 ,2 ,9 ]
Miedema, Frank [1 ,2 ]
机构
[1] Univ Med Ctr, Dept Immunol, NL-3508 AB Utrecht, Netherlands
[2] Sanquin Res & Acad Med Ctr, Amsterdam, Netherlands
[3] Univ Med Ctr, Dept Internal Med, NL-3508 AB Utrecht, Netherlands
[4] Univ Amsterdam, Acad Med Ctr, Dept Internal Med, Div Infect Dis Trop Med & AIDS, NL-1105 AZ Amsterdam, Netherlands
[5] Int Antiviral Therapy Evaluat Ctr, Amsterdam, Netherlands
[6] Univ Amsterdam, Acad Med Ctr, Dept Paediat, NL-1105 AZ Amsterdam, Netherlands
[7] Univ Med Ctr, Dept Paediat Infect Dis, NL-3508 AB Utrecht, Netherlands
[8] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada
[9] Univ Utrecht, Utrecht, Netherlands
关键词
D O I
10.4049/jimmunol.181.2.1573
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
It remains uncertain whether full T cell reconstitution can be established in HIV-infected children and adults with long-term sustained virological control by highly active antiretroviral therapy (HAART). In this study, we comprehensively analyzed various phenotypical markers of CD4 T cell recovery. In addition to measuring T cell activation and proliferation markers, CD4 T cell generation and aging of the CD4 T cell compartment were assessed by measuring TCR excision circles and the fraction of CD31-expressing naive CD4 T cells. In all children and in adults with relatively high CD4 T cell counts at start of therapy (>200 cells/mu l), total CD4 T cell numbers normalized within I year of therapy. After long-term HAART (4.4-9.6 years), naive CD4 T cell counts had normalized in both groups. Although in adults with low baseline CD4 T cell counts (<200 cells/mu l) total CD4 T cell numbers normalized eventually after at least 7 years of HAART, naive CD4 T cell counts had still not recovered. TCR excision circle data showed that thymic T cell production contributed to naive T cell recovery at all ages. The fraction of CD31-expressing naive CD4 T cells was found to be normal, suggesting that the CD4 T cell repertoire was diverse after long-term HAART. Hence, under sustained viral suppression during long-term HAART, the T cell compartment has the potential to fully recover by generating new naive T cells both in children and in adults with high baseline CD4 T cells counts. Irrespective of baseline CD4 T cell counts, reconstitution occurred without a significant effect on T cell aging as reflected by markers for replicative history.
引用
收藏
页码:1573 / 1581
页数:9
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