title: Decreased apoptosis despite severe CD4 depletion in the thymus of a human immunodeficiency virus-1 infected child.
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.
authors.affiliation: Pediatrics, Innsbruck Medical University, Anichstrasse 35, Innsbruck, Austria. juergen.brunner@uki.at
authors.forename: J
authors.initials: J
authors.lastname: Brunner
authors.forename: T
authors.initials: T
authors.lastname: Boehler
authors.forename: V
authors.initials: V
authors.lastname: Ehemann
authors.forename: S
authors.initials: S
authors.lastname: Kassam
authors.forename: H
authors.initials: H
authors.lastname: Otto
authors.forename: C
authors.initials: C
authors.lastname: Sergi
mesh_terms: D017209:Apoptosis / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002648:Child; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D013950:Thymus Gland / Q000276:immunology* / Q000473:pathology