BACKGROUND: Human cytomegalovirus infection is the most frequent viral complication in patients undergoing hematopoietic stem cell transplantation. We investigated the development of human cytomegalovirus-specific T cells in adult recipients of hematopoietic stem cell transplants. DESIGN AND METHODS: From May 2003 through October 2006 a total of 45 patients were monitored for human cytomegalovirus-specific T-cell reconstitution. Human cytomegalovirus-infected autologous dendritic cells were used as a stimulus to detect interferon-gamma-producing human cytomegalovirus-specific CD8(+) and CD4(+) T cells during the first year after transplantation. Interleukin-2 production by specific T cells was also determined. RESULTS: Human cytomegalovirus infection was detected in the blood of 39/45 patients at a median of 29 days after transplantation. Human cytomegalovirus-specific T-cell reconstitution followed reactivation of latent human cytomegalovirus infection at a median time of about 2 months after transplantation. Only donor human cytomegalovirus-seronegativity and bone marrow as a stem cell source were found to delay specific T-cell reconstitution significantly. Levels of three CD8(+) and one CD4(+) human cytomegalovirus-specific T-cells/microL blood had a positive predictive value of around 80% for identifying patients able to control human cytomegalovirus infection spontaneously. Five patients who received high doses of steroids for treatment of graft-versus-host disease developed human cytomegalovirus infection requiring pre-emptive treatment despite high levels of interferon-gamma-producing T cells in response to human cytomegalovirus. Specific interleukin-2 production was not detected in patients with human cytomegalovirus infection requiring treatment, while 90% of patients who spontaneously controlled human cytomegalovirus infection had T cells that produced interleukin-2 and interferon-gamma. CONCLUSIONS: Pre-transplant human cytomegalovirus infection of the recipient is a major factor driving human cytomegalovirus-specific immune reconstitution. Control of human cytomegalovirus infection likely requires the presence of both interferon-gamma and interleukin-2 producing T cells. Corticosteroid treatment may favor active viral replication even in patients with specific T cells.
BACKGROUND: Human cytomegalovirus infection is the most frequent viral complication in patients undergoing hematopoietic stem cell transplantation. We investigated the development of human cytomegalovirus-specific T cells in adult recipients of hematopoietic stem cell transplants. DESIGN AND METHODS: From May 2003 through October 2006 a total of 45 patients were monitored for human cytomegalovirus-specific T-cell reconstitution. Human cytomegalovirus-infected autologous dendritic cells were used as a stimulus to detect interferon-gamma-producing human cytomegalovirus-specific CD8(+) and CD4(+) T cells during the first year after transplantation. Interleukin-2 production by specific T cells was also determined. RESULTS: Human cytomegalovirus infection was detected in the blood of 39/45 patients at a median of 29 days after transplantation. Human cytomegalovirus-specific T-cell reconstitution followed reactivation of latent human cytomegalovirus infection at a median time of about 2 months after transplantation. Only donorhuman cytomegalovirus-seronegativity and bone marrow as a stem cell source were found to delay specific T-cell reconstitution significantly. Levels of three CD8(+) and one CD4(+) human cytomegalovirus-specific T-cells/microL blood had a positive predictive value of around 80% for identifying patients able to control human cytomegalovirus infection spontaneously. Five patients who received high doses of steroids for treatment of graft-versus-host disease developed human cytomegalovirus infection requiring pre-emptive treatment despite high levels of interferon-gamma-producing T cells in response to human cytomegalovirus. Specific interleukin-2 production was not detected in patients with human cytomegalovirus infection requiring treatment, while 90% of patients who spontaneously controlled human cytomegalovirus infection had T cells that produced interleukin-2 and interferon-gamma. CONCLUSIONS: Pre-transplant human cytomegalovirus infection of the recipient is a major factor driving human cytomegalovirus-specific immune reconstitution. Control of human cytomegalovirus infection likely requires the presence of both interferon-gamma and interleukin-2 producing T cells. Corticosteroid treatment may favor active viral replication even in patients with specific T cells.
Authors: Joanna M Schaenman; Sumana Shashidhar; Chanu Rhee; Jonathan Wong; Shelly Navato; Ruby M Wong; Dora Y Ho; Sally Arai; Laura Johnston; Janice M Brown Journal: Biol Blood Marrow Transplant Date: 2010-08-22 Impact factor: 5.742
Authors: S-K Tey; M P Davenport; G R Hill; G A Kennedy; S T Durrant; R Khanna; D Cromer Journal: Bone Marrow Transplant Date: 2014-11-17 Impact factor: 5.483
Authors: Abraham Guerrero; Stanley R Riddell; Jan Storek; Terry Stevens-Ayers; Barry Storer; John A Zaia; Stephen Forman; Robert S Negrin; Thomas Chauncey; William Bensinger; Michael Boeckh Journal: Biol Blood Marrow Transplant Date: 2011-05-20 Impact factor: 5.742
Authors: Helen L Wu; Whitney C Weber; Christine Shriver-Munsch; Tonya Swanson; Mina Northrup; Heidi Price; Kimberly Armantrout; Mitchell Robertson-LeVay; Jason S Reed; Katherine B Bateman; Eisa Mahyari; Archana Thomas; Stephanie L Junell; Theodore R Hobbs; Lauren D Martin; Rhonda MacAllister; Benjamin N Bimber; Mark K Slifka; Alfred W Legasse; Cassandra Moats; Michael K Axthelm; Jeremy Smedley; Anne D Lewis; Lois Colgin; Gabrielle Meyers; Richard T Maziarz; Benjamin J Burwitz; Jeffrey J Stanton; Jonah B Sacha Journal: Xenotransplantation Date: 2020-01-13 Impact factor: 3.907