Vulnerability to reservoir reseeding due to high immune activation after allogeneic hematopoietic stem cell transplantation in individuals with HIV-1 - Archive ouverte HAL Access content directly
Journal Articles Science Translational Medicine Year : 2020

Vulnerability to reservoir reseeding due to high immune activation after allogeneic hematopoietic stem cell transplantation in individuals with HIV-1

(1, 2) , (3) , (3) , (4) , (3) , (5) , (6) , (6) , (7) , (7) , (8) , (9) , (10) , (11) , (1, 12) , (13) , (14) , (15, 16) , (15, 16) , (15, 16) , (15, 16) , (14) , (14) , (4, 17, 18) , (1, 2) , (3)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
Jürgen H E Kuball
  • Function : Author
  • PersonId : 996153

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 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.
Fichier principal
Vignette du fichier
aay9355_ArticleContent_v5 ASC clean2.pdf (7.77 Mo) Télécharger le fichier
Origin : Files produced by the author(s)
Loading...

Dates and versions

pasteur-02870497 , version 1 (16-06-2020)

Identifiers

Cite

Johanna M Eberhard, Mathieu Angin, Caroline Passaes, Maria Salgado, Valerie Monceaux, et al.. Vulnerability to reservoir reseeding due to high immune activation after allogeneic hematopoietic stem cell transplantation in individuals with HIV-1. Science Translational Medicine, 2020, 12 (542), pp.eaay9355. ⟨10.1126/scitranslmed.aay9355⟩. ⟨pasteur-02870497⟩

Collections

PASTEUR
183 View
365 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More