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Single-cell T-cell receptor-β analysis of HLA-A*2402-restricted CMV- pp65-specific cytotoxic T-cells in allogeneic hematopoietic SCT

2013; Springer Nature; Volume: 49; Issue: 1 Linguagem: Inglês

10.1038/bmt.2013.122

1476-5365

Hideki Nakasone, Y Tanaka, Rie Yamazaki, Kiriko Terasako, Miki Sato, Kana Sakamoto, Ryo Yamasaki, Hidenori Wada, Yu Ishihara, Koji Kawamura, Tomohito Machishima, Masahiro Ashizawa, S-i Kimura, Misato Kikuchi, Aki Tanihara, Junya Kanda, Shinichi Kako, Junji Nishida, Yoshinobu Kanda,

Immune Cell Function and Interaction

Cellular immunity is important for the control of CMV infection after allogeneic hematopoietic cell transplantation (Allo-HCT). However, the actual in vivo dynamics of CMV-specific cytotoxic T cell (CMV-CTL) clones are still unclear. We conducted clone monitoring of tetramer+ CMV-CTLs in HLA-A*2402-positive donor–patient pairs, using a direct single-cell analysis that enabled the simultaneous identification and quantification of CTL clones. Clone dynamics were assessed in three cases with or without CMV reactivation. In Case-1 without CMV reactivation, despite the long-term use of systemic steroid, dominant clones of Donor-1 persisted and remained dominant. The CMV-CTLs at 1 year after Allo-HCT included a high proportion of CD45RA+CCR7− effector and CD27−CD57+mature T cells. On the other hand, in Cases-2 and -3 with CMV reactivation, novel clones appeared and became dominant during the follow-up. Their CMV-CTLs included more CD27+ immature T cells at 1 year after Allo-HCT. With regard to clonotypes, HLA-A*2402-restricted CMV-CTLs tended to select BV7 and BJ1-1 genes for complementarity-determining region 3 (CDR3) of T-cell receptor (TCR)-β. Specific amino-acid sequences of CDR3 of TCR-β were found in each case. Patterns of clone reconstitution and phenotype would be different according to CMV reactivation. In vivo clone monitoring of CMV-CTLs could provide insight into the mechanism of immunological reconstitution following Allo-HCT.