Increased ex vivo cell death of central memory CD4 T cells in treated HIV infected individuals with unsatisfactory immune recovery
Massanella Luna, Marta, 1983- (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Gomez, Elisabet (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Carrillo, Jorge (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Curriu Martí, Marta (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Ouchi, Dan (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Puig, Jordi (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Negredo Puigmal, Eugènia (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Cabrera Navarro, Cecilia (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Clotet Sala, Bonaventura (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Blanco, Julià (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Universitat Autònoma de Barcelona

Data:	2015
Resum:	BACKGROUND: High levels of ex vivo CD4 T-cell death and the accumulation of highly differentiated and/or immunosenescent T cells have been associated with poor CD4 T-cell recovery in treated HIV-infected individuals. However, the relationship between cell death and T-cell differentiation is still unclear. METHODS: We have analyzed cell death, immunosenescence and differentiation parameters in HAART-treated subjects (VL <50 copies/mL for more than 2 years) with CD4 T-cell count <350 cells/μL (immunodiscordant, n = 23) or >400 cells/μL (immunoconcordant, n = 33). We included 11 healthy individuals as reference. RESULTS: As expected, suboptimal CD4 T-cell recovery was associated with low frequencies of naïve cells, high frequencies of transitional and effector memory cells and a subsequent low ratio of central/transitional memory cells in the CD4 compartment. These alterations correlated with spontaneous CD4 T-cell death. A deeper analysis of cell death in CD4 T-cell subsets showed increased cell death in memory cells of immunodiscordant individuals, mainly affecting central memory cells. Immunosenescence was also higher in immunodiscordant individuals albeit unrelated to cell death. The CD8 compartment was similar in both HIV-infected groups, except for an underrepresentation of naïve cells in immunodiscordant individuals. CONCLUSION: Immunodiscordant individuals show alterations in memory CD4 T-cell differentiation associated with a short ex vivo lifespan of central memory cells and an in vivo low central/transitional memory cell ratio. These alterations may contribute to poor CD4 T-cell repopulation.
Ajuts:	Instituto de Salud Carlos III RD12/0017/0002
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Immunodiscordant ; Cell death ; T‑cell subsets ; Immunosenescence ; HAART ; Cart
Publicat a:	Journal of translational medicine, Vol. 13 (July 2015) , article 33, ISSN 1479-5876

DOI: 10.1186/s12967-015-0601-2
PMID: 26183947

11 p, 1.1 MB

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