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  • Title: Decreased apoptosis despite severe CD4 depletion in the thymus of a human immunodeficiency virus-1 infected child.
    Author: Brunner J, Boehler T, Ehemann V, Kassam S, Otto H, Sergi C.
    Journal: Klin Padiatr; 2011 Jul; 223(4):246-8. PubMed ID: 21271506.
    Abstract:
    Thymic epithelial space (TES), where thymopoiesis is located, and thymic perivascular space (PVS), where T lymphocytes are pooled, appear differentially involved in human immunodeficiency virus 1 (HIV-1)-infected children. The decline of CD4+ T cells during HIV-1 infection is probably due to a relative predominance of CD4+ T cell destruction on cell proliferation. Antiretroviral therapy (ART) typically increases circulating CD4+ T cell counts, but it is debated whether ART reduces the destruction of existing CD4+ T cells or enhances the production of new cells. We report on postmortem flow-cytometry, immunohistochemistry, and terminal deoxynucleotide transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) studies performed on thymus of an 11-year-old vertically HIV-1 infected child receiving ART. Thymus tissue sections showed that CD4+ and CD8+ cells were more numerous in PVS than in TES (p=0.0334 for CD4+ cells, p<0.0001 for CD8+ cells). Thymus cell suspension showed that CD4+ CD8+ cells (immature thymocytes) were 15.4% (age-related control: 80.5%). Very few apoptotic CD4+ cells were seen in TES. Very low to absent proliferation activity was demonstrated in both TES and PVS. We suggest that 1) lymphocyte depletion in HIV-1 infection is more pronounced in TES than in PVS, 2) immature thymocytes are not enhanced, and 3) an anti-apoptotic effect in the thymus seems to be a potential ART mechanism to explain the CD4+ pool increase.
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