title: Loss of immune homeostasis dictates SHIV rebound after stem-cell transplantation.
abstract: The conditioning regimen used as part of the Berlin patient's hematopoietic cell transplant likely contributed to his eradication of HIV infection. We studied the impact of conditioning in simian-human immunodeficiency virus-infected (SHIV-infected) macaques suppressed by combination antiretroviral therapy (cART). The conditioning regimen resulted in a dramatic, but incomplete depletion of CD4+and CD8+T cells and CD20+B cells, increased T cell activation and exhaustion, and a significant loss of SHIV-specific Abs. The disrupted T cell homeostasis and markers of microbial translocation positively correlated with an increased viral rebound after cART interruption. Quantitative viral outgrowth and Tat/rev-induced limiting dilution assays showed that the size of the latent SHIV reservoir did not correlate with viral rebound. These findings identify perturbations of the immune system as a mechanism for the failure of autologous transplantation to eradicate HIV. Thus, transplantation strategies may be improved by incorporating immune modulators to prevent disrupted homeostasis, and gene therapy to protect transplanted cells.
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.|Department of Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Peterson
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Clarisse
authors.initials: C
authors.lastname: Benne
authors.affiliation: Washington National Primate Research Center, Seattle, Washington, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Polacino
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Jasbir
authors.initials: J
authors.lastname: Kaur
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Cristina E
authors.initials: CE
authors.lastname: McAllister
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Abdelali
authors.initials: A
authors.lastname: Filali-Mouhim
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Willi
authors.initials: W
authors.lastname: Obenza
authors.affiliation: Washington National Primate Research Center, Seattle, Washington, USA.
authors.forename: Tiffany A
authors.initials: TA
authors.lastname: Pecor
authors.affiliation: Division of Vaccine and Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Meei-Li
authors.initials: ML
authors.lastname: Huang
authors.affiliation: Washington National Primate Research Center, Seattle, Washington, USA.
authors.forename: Audrey
authors.initials: A
authors.lastname: Baldessari
authors.affiliation: Washington National Primate Research Center, Seattle, Washington, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Murnane
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.|Department of Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Ann E
authors.initials: AE
authors.lastname: Woolfrey
authors.affiliation: Division of Vaccine and Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.|Department of Laboratory Medicine.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Jerome
authors.affiliation: Washington National Primate Research Center, Seattle, Washington, USA.|Department of Pharmaceutics and.
authors.forename: Shiu-Lok
authors.initials: SL
authors.lastname: Hu
authors.affiliation: Washington National Primate Research Center, Seattle, Washington, USA.|Department of Pharmaceutics and.
authors.forename: Nichole R
authors.initials: NR
authors.lastname: Klatt
authors.affiliation: Division of Vaccine and Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: DeRosa
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Rafick P
authors.initials: RP
authors.lastname: Sékaly
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.|Department of Medicine, University of Washington, Seattle, Washington, USA.|Department of Pathology, University of Washington, Seattle, Washington, USA.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Kiem
mesh_terms: D000818:Animals; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000528:radiation effects*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000528:radiation effects*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000528:radiation effects*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006706:Homeostasis / Q000528:radiation effects; D016180:Lentivirus Infections / Q000188:drug therapy / Q000276:immunology; D008254:Macaca nemestrina; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000528:radiation effects*; D019172:Transplantation Conditioning / Q000379:methods*; D014182:Transplantation, Autologous; D019562:Viral Load / Q000528:radiation effects; D014916:Whole-Body Irradiation
chemical_list: D044966:Anti-Retroviral Agents