Single-cell T-cell receptor-β analysis of HLA-A*2402-restricted CMV- pp65-specific cytotoxic T-cells in allogeneic hematopoietic SCT.
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.
Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
H
H
Nakasone
Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
Y
Y
Tanaka
Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
R
R
Yamazaki
Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
K
K
Terasako
Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
M
M
Sato
Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
K
K
Sakamoto
Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
R
R
Yamasaki
Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
H
H
Wada
Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
Y
Y
Ishihara
Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
K
K
Kawamura
Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
T
T
Machishima
Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
M
M
Ashizawa
Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
S-I
SI
Kimura
Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
M
M
Kikuchi
Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
A
A
Tanihara
Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
J
J
Kanda
Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
S
S
Kako
Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
J
J
Nishida
Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
Y
Y
Kanda
D000293:Adolescent; D000328:Adult; D018959:CD57 Antigens / Q000378:metabolism; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections / Q000276:immunology; D005260:Female; D059871:HLA-A24 Antigen / Q000378:metabolism*; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D010641:Phenotype; D010750:Phosphoproteins / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D054400:Receptors, CCR7 / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014184:Transplantation, Homologous; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000276:immunology*; D055815:Young Adult
C515370:CCR7 protein, human; D018959:CD57 Antigens; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen; D010750:Phosphoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054400:Receptors, CCR7; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa