Eberhard, Johanna M., Angin, Mathieu ORCID: 0000-0002-6867-4680, Passaes, Caroline ORCID: 0000-0002-0813-2521, Salgado, Maria, Monceaux, Valerie, Knops, Elena, Kobbe, Guido, Jensen, Bjoern, Christopeit, Maximilian ORCID: 0000-0003-4627-0412, Kroeger, Nicolaus, Vandekerckhove, Linos, Badiola, Jon, Bandera, Alessandra, Raj, Kavita ORCID: 0000-0002-8258-354X, van Lunzen, Jan, Huetter, Gero, Kuball, Juergen H. E., Martinez-Laperche, Carolina, Balsalobre, Pascual, Kwon, Mi ORCID: 0000-0002-3855-7774, Diez-Martin, Jose L., Nijhuis, Monique, Wensing, Annemarie, Martinez-Picado, Javier ORCID: 0000-0002-4916-2129, Schulze Zur Wiesch, Julian and Saez-Cirion, Asier ORCID: 0000-0003-2406-7536 (2020). Vulnerability to reservoir reseeding due to high immune activation after allogeneic hematopoietic stem cell transplantation in individuals with HIV-1. Sci. Transl. Med., 12 (542). WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE. ISSN 1946-6242

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Abstract

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 CCR5432/432 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Eberhard, Johanna M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Angin, MathieuUNSPECIFIEDorcid.org/0000-0002-6867-4680UNSPECIFIED
Passaes, CarolineUNSPECIFIEDorcid.org/0000-0002-0813-2521UNSPECIFIED
Salgado, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Monceaux, ValerieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knops, ElenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kobbe, GuidoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jensen, BjoernUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Christopeit, MaximilianUNSPECIFIEDorcid.org/0000-0003-4627-0412UNSPECIFIED
Kroeger, NicolausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vandekerckhove, LinosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Badiola, JonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bandera, AlessandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Raj, KavitaUNSPECIFIEDorcid.org/0000-0002-8258-354XUNSPECIFIED
van Lunzen, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huetter, GeroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuball, Juergen H. E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martinez-Laperche, CarolinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Balsalobre, PascualUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kwon, MiUNSPECIFIEDorcid.org/0000-0002-3855-7774UNSPECIFIED
Diez-Martin, Jose L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nijhuis, MoniqueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wensing, AnnemarieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martinez-Picado, JavierUNSPECIFIEDorcid.org/0000-0002-4916-2129UNSPECIFIED
Schulze Zur Wiesch, JulianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saez-Cirion, AsierUNSPECIFIEDorcid.org/0000-0003-2406-7536UNSPECIFIED
URN: urn:nbn:de:hbz:38-334329
DOI: 10.1126/scitranslmed.aay9355
Journal or Publication Title: Sci. Transl. Med.
Volume: 12
Number: 542
Date: 2020
Publisher: AMER ASSOC ADVANCEMENT SCIENCE
Place of Publication: WASHINGTON
ISSN: 1946-6242
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
T-CELLS; HEPATITIS-B; BONE-MARROW; PROGRAMMED DEATH-1; VIRAL-INFECTION; RECONSTITUTION; DISEASE; RECIPIENTS; CYTOMEGALOVIRUS; MEMORYMultiple languages
Cell Biology; Medicine, Research & ExperimentalMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/33432

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