title: Early detection of cytomegalovirus-specific cytotoxic T lymphocytes against cytomegalovirus antigenemia in human leukocyte antigen haploidentical hematopoietic stem cell transplantation.
abstract: Human leukocyte antigen (HLA)-haploidentical stem cell transplantation (haplo-SCT) is associated with a high incidence of cytomegalovirus (CMV) infection, probably originating from the delayed reconstitution of CMV-specific T cell immunity. There have been few reports on the presence of CMV-specific cytotoxic T lymphocytes (CMV-CTLs) after haplo-SCT. We have studied CMV-specific immune reconstitution by measuring the absolute number of CMV-CTLs using a flow cytometry method with HLA-A2-restricted NLVPMVATV peptide dextramers. We examined the association between reconstitution patterns of CMV-CTLs and the duration of CMV antigenemia in 15 patients who underwent first allogeneic SCT from HLA-haploidentical-related donors with HLA-A2. In seven and eight patients, CMV antigenemia consecutively resolved for more than 4 weeks (the CMV antigenemia 'resolved' group) and intermittently persisted (the CMV antigenemia 'persistent' group) during a 100-day observation period, respectively. The group of the seven patients, in whom levels of CMV antigenemia were reduced to zero, had a significantly lower maximum level of CMV antigenemia than the CMV antigenemia persistent group. In contrast, the CMV antigenemia persistent group had a significantly higher maximum level of CMV-CTLs, but the levels took longer to peak. Despite no difference in general lymphocyte recovery between the two groups, the CMV antigenemia resolved group had significantly higher median CMV-CTL counts than the CMV antigenemia persistent group at 6 weeks after onset of CMV infection. Flow cytometry analysis of CMV-CTLs is a convenient method of monitoring reconstitution of CMV-specific lymphocyte immunity following haplo-SCT.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya City, Hyogo, 663-8501, Japan, kato.ruri@k.nissay-hp.or.jp.
authors.forename: Ruri
authors.initials: R
authors.lastname: Kato
authors.forename: Hiroya
authors.initials: H
authors.lastname: Tamaki
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ikegame
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshihara
authors.forename: Katsuji
authors.initials: K
authors.lastname: Kaida
authors.forename: Kyoko
authors.initials: K
authors.lastname: Taniguchi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Inoue
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ishii
authors.forename: Jun
authors.initials: J
authors.lastname: Nakata
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fujioka
authors.forename: Ryoji
authors.initials: R
authors.lastname: Eguchi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Soma
authors.forename: Masaya
authors.initials: M
authors.lastname: Okada
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D000328:Adult; D003587:Cytomegalovirus / Q000276:immunology* / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000175:diagnosis* / Q000276:immunology* / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006680:HLA Antigens / Q000276:immunology*; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015996:Survival Rate / Q000639:trends; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D014184:Transplantation, Homologous
chemical_list: D006680:HLA Antigens