TCR spectratyping revealed T lymphocytes associated with graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.
Clonal expansion of T cells after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been observed, but their characteristics remain to be fully elucidated. We report here that CD8(+) T cells were the dominant T lymphocytes seen and T-cell repertoire diversity decreased dramatically during the first 3 months after allo-HSCT. Patients with GVHD grade II - IV had significantly lower T-cell repertoire diversity compared with non-GVHD patients. TCR beta variable gene (TCRBV) subfamily 8, 5.1, 5.2, 4, and 13 were the five most frequently expanded subfamilies among these patients. Among the 49 over-expanded clones identified, clonotype "TCR3-5" and "TCR18-5" were isolated from four patients with HLA-A2 allele and skin GVHD. Their frequencies correlated well with skin symptoms (i.e. rash). Moreover, they were detected in donors but not detected in recipients before transplantation. Lastly, three common TCRBV CDR3 motifs shared by T cells related with GVHD were discovered: TGDS, GLAG, and GGG. These findings suggest that TCR spectratyping is helpful for revealing GVHD-related T cells and may have utility in early diagnosis.
Du
Jin-Wei
JW
Department of Hematology, Peking University First Hospital, West District, Beijing, China.
Gu
Jiang-Ying
JY
Liu
Jing
J
Cen
Xi-Nan
XN
Zhang
Ying
Y
Ou
Yuan
Y
Chu
Bin
B
Zhu
Ping
P
D000293:Adolescent; D000328:Adult; D020816:Amino Acid Motifs; D018414:CD8-Positive T-Lymphocytes; D002648:Child; D022801:Complementarity Determining Regions / Q000032:analysis; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis* / Q000276:immunology; D020544:Graft vs Leukemia Effect / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007135:Immunoglobulin Variable Region; D007938:Leukemia / Q000628:therapy; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous
D022801:Complementarity Determining Regions; D017931:DNA Primers; D007135:Immunoglobulin Variable Region; D011948:Receptors, Antigen, T-Cell