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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Vulnerability to reservoir reseeding due to high immune activation after allogeneic hematopoietic stem cell transplantation in individuals with HIV-1
Science Translational Medicine, Volume 12, No. 542, Article eaay9355, Year 2020
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Description
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only medical intervention that has led to an HIV cure. Whereas the HIV reservoir sharply decreases after allo-HSCT, the dynamics of the T cell reconstitution has not been comprehensively described. We analyzed the activation and differentiation of CD4+ and CD8+ T cells, and the breadth and quality of HIV- and CMV-specific CD8+ T cell responses in 16 patients with HIV who underwent allo-HSCT (including five individuals who received cells from CCR5Δ32/Δ32 donors) to treat their underlying hematological malignancy and who remained on antiretroviral therapy (ART). We found that reconstitution of the T cell compartment after allo-HSCT was slow and heterogeneous with an initial expansion of activated CD4+ T cells that preceded the expansion of CD8+ T cells. Although HIV-specific CD8+ T cells disappeared immediately after allo-HSCT, weak HIV-specific CD8+ T cell responses were detectable several weeks after transplant and could still be detected at the time of full T cell chimerism, indicating that de novo priming, and hence antigen exposure, occurred during the time of T cell expansion. These HIV-specific T cells had limited functionality compared with CMV-specific CD8+ T cells and persisted years after allo-HSCT. In conclusion, immune reconstitution was slow, heterogeneous, and incomplete and coincided with de novo detection of weak HIV-specific T cell responses. The initial short phase of high T cell activation, in which HIV antigens were present, may constitute a window of vulnerability for the reseeding of viral reservoirs, emphasizing the importance of maintaining ART directly after allo-HSCT. © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Authors & Co-Authors
Eberhard, Johanna Maria
Germany, Hamburg
Universitätsklinikum Hamburg-eppendorf
Germany, Hamburg
German Center for Infection Research Dzif, Partner Site Hamburg
Angin, Mathieu
France, Paris
Institut Pasteur, Paris
Passaes, Caroline
France, Paris
Institut Pasteur, Paris
Salgado, María
Spain, Badalona
Irsicaixa Aids Research Institute
Monceaux, Valérie
France, Paris
Institut Pasteur, Paris
Knops, Elena
Germany, Koln
Universität zu Köln
Kobbe, Guido
Germany, Dusseldorf
Universitätsklinikum Düsseldorf
Jensen, Björn Erik Ole
Germany, Dusseldorf
Universitätsklinikum Düsseldorf
Christopeit, Maximilian
Germany, Hamburg
Universitätsklinikum Hamburg-eppendorf
Kröger, Nikolaus Martin
Germany, Hamburg
Universitätsklinikum Hamburg-eppendorf
Vandekerckhove, Linos P.R.
Belgium, Ghent
Universiteit Gent
Bandera, Alessandra
Italy, Milan
Università Degli Studi Di Milano-bicocca
Raj, Kavita Shrivastava
United Kingdom, London
Ucl Cancer Institute
van Lunzen, Jan
Germany, Hamburg
Universitätsklinikum Hamburg-eppendorf
United Kingdom, Brentford
Viiv Healthcare
Díez-Martín, José Luís
Spain, Madrid
Hospital General Universitario Gregorio Marañón
Nijhuis, Monique M.
Netherlands, Utrecht
University Medical Center Utrecht
Wensing, Annemarie Marie J.
Netherlands, Utrecht
University Medical Center Utrecht
Martínez-Picado, Javier
Spain, Badalona
Irsicaixa Aids Research Institute
Spain, Vic
Universitat de Vic - Universitat Central de Catalunya Uvic-ucc
Spain, Barcelona
Institució Catalana de Recerca I Estudis Avançats
Schulze-Zur-Wiesch, Julian
Germany, Hamburg
Universitätsklinikum Hamburg-eppendorf
Germany, Hamburg
German Center for Infection Research Dzif, Partner Site Hamburg
Sáez-Cirión, Asier
France, Paris
Institut Pasteur, Paris
Statistics
Citations: 16
Authors: 20
Affiliations: 16
Identifiers
Doi:
10.1126/SCITRANSLMED.AAY9355
ISSN:
19466234
Research Areas
Infectious Diseases
Study Design
Randomised Control Trial