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

  1. 1Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
  2. 2Department of Hematology and Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
  3. 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.

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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/mul) and those who did not (12/mul). Serial tetramer analysis showed that 21% of the patients had >10/mul CMV-specific CTL at the first detection of CMV antigenemia and 67% of the patients had more than 10/mul 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-gamma producing CD4+ and CD8+ lymphocytes were suppressed at the onset of CMV colitis (1.6 and 8/mul), which increased with recovery of the disease (19 and 47/mul). 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-gamma, CTL, HSCT, HLA-A02

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