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

N Vrisekoop, R van Gent, AB de Boer… - The Journal of …, 2008 - journals.aai.org
N Vrisekoop, R van Gent, AB de Boer, SA Otto, JCC Borleffs, R Steingrover, JM Prins…
The Journal of Immunology, 2008journals.aai.org
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 …
Abstract
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/μl), total CD4 T cell numbers normalized within 1 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/μl) 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.
journals.aai.org