1. Homeostatic Expansion of CD4+ T Cells Promotes Cortical and Trabecular Bone Loss, Whereas CD8+ T Cells Induce Trabecular Bone Loss Only.
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Weitzmann, M. Neale, Vikulina, Tatyana, Roser-Page, Susanne, Yamaguchi, Masayoshi, and Ofotokun, Ighovwerha
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T cells , *CD4 antigen , *HIV infections , *ANTIRETROVIRAL agents , *IMMUNODEFICIENCY , *BONE density , *ANIMAL experimentation , *BONE resorption , *MICE , *OSTEOPOROSIS , *ANTI-HIV agents , *IN vitro studies , *PHYSIOLOGY - Abstract
Background: Bone loss occurs in human immunodeficiency virus (HIV) infection but paradoxically is intensified by HIV-associated antiretroviral therapy (ART), resulting in an increased fracture incidence that is largely independent of ART regimen. Inflammation in the bone microenvironment associated with T-cell repopulation following ART initiation may explain ART-induced bone loss. Indeed, we have reported that reconstitution of CD3+ T cells in immunodeficient mice mimics ART-induced bone loss observed in humans. In this study, we quantified the relative effects of CD4+ and CD8+ T-cell subsets on bone.Methods: T-cell subsets in T-cell receptor β knockout mice were reconstituted by adoptive transfer with CD4+ or CD8+ T-cells subsets were reconstituted in T-cell receptor β knockout mice by adoptive transfer, and bone turnover, bone mineral density, and indices of bone structure and turnover were quantified.Results: Repopulating CD4+ but not CD8+ T cells significantly diminished bone mineral density. However, micro-computed tomography revealed robust deterioration of trabecular bone volume by both subsets, while CD4+ T cells additionally induced cortical bone loss.Conclusions: CD4+ T-cell reconstitution, a key function of ART, causes significant cortical and trabecular bone loss. CD8+ T cells may further contribute to trabecular bone loss in some patients with advanced AIDS, in whom CD8+ T cells may also be depleted. Our data suggest that bone densitometry used for assessment of the condition of bone in humans may significantly underestimate trabecular bone damage sustained by ART. [ABSTRACT FROM AUTHOR]- Published
- 2017
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