Changes in the T-cell receptor V beta gene repertoire after allogeneic hematopoietic stem cell transplantation.
BACKGROUND
We distinguished graft-versus-host disease (GVHD) from graft-versus-leukemia (GVL) effects and to investigate the distribution of T-cell receptor (TCR) V beta gene repertoire in individuals with leukemia before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT).


METHODS
Peripheral blood mononuclear cells (PBMC) were obtained from 10 normal individuals, 8 donors and 11 patients with leukemia before and after transplantation. Polymerase chain reaction (PCR) amplification of complementarity-determining region 3 (CDR3) of 24 TCR V beta genes was used to examine serial samples of PBMC. The PCR products were further analyzed by genescan to evaluate clonality of T cells.


RESULTS
The 24 TCR V beta gene repertoire displayed highly diverse and polyclonal spectratypes in all normal individuals and 4 of 8 donors. Another 4 donors expressed part of the 24 TCR V beta subfamily and 1 donor had oligoclonality. The expressions of the 24 TCR V beta subfamilies were skewed and restricted in 11 leukemia patients before and after transplantation. Some absences of 24 TCR V beta subfamily expression were quite similar between the recipients pro-transplantation and related donors. The number of subfamilies expressed increased over time post-transplantation, but the restricted expressions of the subfamily could last 6 - 30 months after transplantation. All patients with GVHD and some without GVHD exhibited T cell clonal expansion. The expansive T cell clone was distributed in V beta 2-3, 16-17, 18-19, 21 and V beta 23 in patients with GVHD and in V beta 7, 9, 16 and 19 in patients without GVHD. One patient with syngeneic-HSCT (syn-HSCT) had V beta 15 and 16 T cell expansion after transplantation. One patient displayed V beta 18 T cell expansion after donor lymphocyte infusion (DLI).


CONCLUSIONS
Normal individuals express the entire 24 TCR V beta gene repertoire and have polyclonal distribution. However, the TCR V beta gene repertoire is only partially expressed in some donors. The TCR V beta gene repertoire is restrictedly expressed in a skew fashion in patients with leukemia before and after transplantation. The number of TCR V beta gene subfamilies increases over time post-transplantation. GVHD and GVL effects may induce the proliferation of T cell clones. Clinical GVL response may be distinguished from GVHD alloreactivity through the host MHC antigen.
Liu
Qi-fa
QF
Department of Hematology, Nanfang Hospital, First Military Medical University, Guangzhou 510515, China. liuqifa@fimmu.com
Li
Yang-qiu
YQ
Yang
Dong
D
Zhang
Yu
Y
Yang
Li-jian
LJ
Chen
Shao-hua
SH
Sun
Jing
J
Liu
Xiao-li
XL
Zhou
Shu-yun
SY
D006086:Graft vs Host Disease / Q000235:genetics*; D020544:Graft vs Leukemia Effect / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000628:therapy; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*
D016693:Receptors, Antigen, T-Cell, alpha-beta