Original Article
Bone Marrow Transplantation (2008) 41, 515–521; doi:10.1038/sj.bmt.1705932; published online 19 November 2007
Functional analysis of cytomegalovirus-specific T lymphocytes compared to tetramer assay in patients undergoing hematopoietic stem cell transplantation
Y Morita-Hoshi1,2, Y Heike1, M Kawakami1, T Sugita3, O Miura2, S-W Kim1, S-I Mori1, T Fukuda1, R Tanosaki1, K Tobinai1 and Y Takaue1
- 1Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
- 2Department of Hematology and Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
- 3Cellular Immunology Section, SRL Inc., Hachioji-city, Tokyo, Japan
Correspondence: Dr Y Takaue, Director, Department of Medical Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. E-mail: ytakaue@ncc.go.jp
Received 7 August 2007; Revised 10 October 2007; Accepted 15 October 2007; Published online 19 November 2007.
Abstract
In order to evaluate whether we could predict reactivation of CMV by monitoring the number of CMV-specific cytotoxic T-lymphocytes (CTL), tetramer analysis was performed in 37 patients who underwent hematopoietic stem cell transplantation (HSCT). The results disclosed that the mean number of CMV-specific CTL at day 30 did not differ among patients who developed CMV antigenemia (22/
l) and those who did not (12/
l). Serial tetramer analysis showed that 21% of the patients had >10/
l CMV-specific CTL at the first detection of CMV antigenemia and 67% of the patients had more than 10/
l CMV-specific CTL at the onset of CMV disease. Intracellular staining upon stimulation by CMV lysates and peptide in patients with CMV colitis revealed that both IFN-
producing CD4+ and CD8+ lymphocytes were suppressed at the onset of CMV colitis (1.6 and 8/
l), which increased with recovery of the disease (19 and 47/
l). These data suggest that it is difficult to predict CMV reactivation solely by the number of CMV-specific CTL. We suggest that additional functional analysis by intracellular cytokine assay may be useful for immunomonitoring against CMV.
Keywords:
CMV, intracellular IFN-
, CTL, HSCT, HLA-A02
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