Reconstitution of HLA-A*2402 - Restricted cytomegalovirus-specific T-cells following stem cell transplantation

Hisashi Gondo, Daisuke Himeji, Kenjiro Kamezaki, Akihiko Numata, Tetsuya Tanimoto, Ken Takase, Kenichi Aoki, Hideho Henzan, Koji Nagafuji, Toshihiro Miyamoto, Fumihiko Ishikawa, Kazuya Shimoda, Shuichi Inaba, Hiroshi Tsukamoto, Takahiko Horiuchi, Hitoshi Nakashima, Takeshi Otsuka, Koji Kato, Mika Kuroiwa, Masakazu HiguchiTsunefumi Shibuya, Tomohiko Kamimura, Kiyotaka Kuzushima, Tatsuya Tsurumi, Yoshinobu Kanda, Mine Harada

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Abstract

Cytomegalovirus (CMV)-specific immune reconstitution early after stem cell transplantation (SCT) was evaluated prospectively by detecting CD8+ T-cells, which recognize the peptide QYDPVAALF in the context of HLA-A*2402. Fifteen allogeneic SCT recipients were included in the study. All recipients and donors were seropositive for CMV and had the HLA-A*2402 allele. CMV-specific T-cells were detected as early as 1 month after transplantation, and their numbers increased to peak levels 2 to 5 months after transplantation. The numbers of CMV-specific T-cells in patients who developed grade II to IV acute graft-versus-host disease (GVHD) and received corticosteroids for acute GVHD were low in the early period after allogeneic SCT. There was a trend toward earlier reconstitution of CMV-specific CD8+ T-cells in allogeneic peripheral blood SCT (PBSCT) patients than in allogeneic bone marrow transplan tation patients. The contribution of T-cells in the graft to the recovery of CMV-specific immune responses was also suggested by the finding that the reconstitution of CMV-specific CD8+ T-cells was delayed in CD34-selected autologous PBSCT compared with unpurged autologous PBSCT. The reconstitution of CMV-specific CD8+ T-cells was delayed in patients with CMV disease or recurrent CMV reactivation. These observations suggest that the detection of CMV-specific T-cells with an HLA-peptide tetramer is useful to assess immune reconstitution against CMV and to identify patients at risk for CMV disease or recurrent CMV reactivation after SCT.

Original languageEnglish
Pages (from-to)441-448
Number of pages8
JournalInternational journal of hematology
Volume80
Issue number5
DOIs
Publication statusPublished - Dec 1 2004

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All Science Journal Classification (ASJC) codes

  • Hematology

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