NK-cell activation is associated with increased HIV transcriptional activity following allogeneic hematopoietic cell transplantation by Louise E. Hogan,

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NK-cell activation is associated with increased HIV transcriptional activity following allogeneic hematopoietic cell transplantation by Louise E. Hogan, Christian Körner, Kristen Hobbs, Camille R. Simoneau, Cassandra Thanh, Erica A. Gibson, Christine D. Palmer, Alisha Pandit, Francisco M. Marty, Daniel R. Kuritzkes, Stephanie Jost, Jerome Ritz, and Timothy J. Henrich BloodAdv Volume 2(12):1412-1416 June 26, 2018 © 2018 by The American Society of Hematology

NK phenotype and response before and after allogeneic HSCT in 3 HIV-infected individuals on suppressive ART. (A) The percentage of lymphocytes that are NK cells, (B) percentage of CD56dimCD16+ NK cells, (C) percentage of CD56−CD16+ NK cells, (D) percentage of CD56brightCD16− NK cells, (E) percentage of CD57+ NK cells, and (F) percentage of NK cells expressing inhibitory KIRs are shown. NK phenotype and response before and after allogeneic HSCT in 3 HIV-infected individuals on suppressive ART. (A) The percentage of lymphocytes that are NK cells, (B) percentage of CD56dimCD16+ NK cells, (C) percentage of CD56−CD16+ NK cells, (D) percentage of CD56brightCD16− NK cells, (E) percentage of CD57+ NK cells, and (F) percentage of NK cells expressing inhibitory KIRs are shown. The percentage of cells expressing a surrogate marker for cytotoxic degranulation (CD107a) and INF-γ in response to MHC-deficient target cells are shown in panels G and H, respectively. Participants (Pt) 1, 2, and 3 experienced decrease in CD4+ T cell-associated HIV-1 DNA levels 5.8, 6.4, and 1 month following HSCT, respectively. Post-HSCT chimerisms for Participants 1, 2, and 3 were 94% donor leukocyte, 89% donor leukocyte (24% Donor T-cell), and 87% donor leukocyte, respectively. M, myeloablative conditioning; RIC, reduced-intensity HSCT conditioning. Louise E. Hogan et al. Blood Adv 2018;2:1412-1416 © 2018 by The American Society of Hematology

Results from a novel ex vivo assay of the effects of NK and CD8+ T-cell responses on HIV laboratory-infected pre-HCT recipient and post-HCT donor-origin CD4+ T cells. Results from a novel ex vivo assay of the effects of NK and CD8+T-cell responses on HIV laboratory-infected pre-HCT recipient and post-HCT donor-origin CD4+T cells. (A) A schema of our assay to determine the effects of allogeneic HSCT on HIV reactivation and effector cell activation and responses is shown. Pre- and post-SCT PBMC were obtained from 30 HIV-uninfected individuals, followed by establishment of latent HIV infection ex vivo in recipient or engrafted donor CD4+ T cells. Post-HSCT donor-derived PBMC were then coincubated with HIV-infected recipient pre-SCT (allogeneic experiments) and donor-derived post-SCT CD4+ T cells (autologous control experiments). (B) An increase in the percent of HIV-reactivated (GFP expressing) proliferating pre-HCT recipient CD4+ T cells was observed in several participant samples following 7 days of coculture (N = 30). Outlier values are shown as individual points on the box plots otherwise representing median and quartile values. Correlations between activated (CD38+/HLA-DR+) donor CD8+ T, NK, and CD3+CD56+ cells and HIV-iGFP–expressing laboratory infected CD4+ T cells on day 7 are shown in panels C (experiments using infected recipient CD4+ T cells and PBMCs following donor cell engraftment) and D (control experiments using infected post-HCT engrafted CD4+ T cells of donor origin), respectively. Significant correlations between NK and CD3+CD56+ cells were identified only in the pre-HCT CD4/post-HCT PBMC experiments, whereas only activated CD8+ T cells correlated with HIV-iGFP expression in the post-HCT CD4/post-HCT PBMC control experiments. Dashed lines represent linear regression and P values were obtained using non-parametric Spearman rank correlation analyses. Louise E. Hogan et al. Blood Adv 2018;2:1412-1416 © 2018 by The American Society of Hematology