Restricted accessResearch articleFirst published online 2014-03
Distribution and Clonality of the Vα and Vβ T-Cell Receptor Repertoire of Regulatory T Cells in Leukemia Patients With and Without Graft Versus Host Disease
Graft versus host disease (GVHD) is the main complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recent data indicated that regulatory T (Treg) cells might relate to GVHD, and such functions might be mediated by certain T-cell receptor (TCR) subfamily of Treg cells. Thus, we analyzed the distribution and clonality of the TCR Vα and Vβ repertoire of Treg cells from leukemia patients with and without GVHD after allo-HSCT. Numerous TCR Vα subfamilies, including Vα1, Vα9, Vα13, Vα16–19, and Vα24–29, were absent in Treg cells after allo-HSCT. The usage numbers for the TCR Vα and Vβ subfamilies in Treg cells from patients without GVHD appeared more widely. The expression frequencies of Vα10 or Vα20 between both groups were significantly different. Moreover, the expression frequency of TCR Vβ2 subfamily in patients without GVHD was significantly higher than that in patients with GVHD. Oligoclonally expanded TCR Vα and Vβ Treg cells were identified in a few samples in both groups. Restricted utilization of the Vα and Vβ subfamilies and the absence of some important TCR rearrangements in Treg cells may be related to GVHD due to a lower regulating function of Treg subfamilies.
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References
1.
BeckR.C., WlodarskiM., GondekL., TheilK.S., TuthillR.J., SobeckR., et al. (2005). Efficient identification of T-cell clones associated with graft-versus-host disease in target tissue allows for subsequent detection in peripheral blood. Br J Haematol, 129, 411–419.
2.
BrownJ.A., and BoussiotisV.A. (2008). Umbilical cord blood transplantation: basic biology and clinical challenges to immune reconstitution. Clin Immunol, 127, 286–297.
3.
DuJ.W., GuJ.Y., LiuJ., CenX.N., ZhangY., OuY., et al. (2007). TCR spectratyping revealed T lymphocytes associated with graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Leuk Lymphoma, 48, 1618–1627.
4.
DvorakC.C., and CowanM.J. (2008). Hematopoietic stem cell transplantation for primary immunodeficiency disease. Bone Marrow Transplant, 41, 119–126.
5.
FohseL., SuffnerJ., SuhreK., WahlB., LindnerC., LeeC.W., et al. (2011). High TCR diversity ensures optimal function and homeostasis of Foxp3+regulatory T cells. Eur J Immunol, 41, 3101–3113.
6.
FriedmanT.M., StattonD., JonesS.C., BergerM.A., MurphyG.F., and KorngoldR. (2001). Vbeta spectratype analysis reveals heterogeneity of CD4+T-cell responses to minor histocompatibility antigens involved in graft-versus-host disease: correlations with epithelial tissue infiltrate. Biol Blood Marrow Transplant, 7, 2–13.
7.
FuY.W., Wu deP., CenJ.N., FengY.F., ChangW.R., ZhuZ.L., et al. (2007). Patterns of T-cell reconstitution by assessment of T-cell receptor excision circle and T-cell receptor clonal repertoire after allogeneic hematopoietic stem cell transplantation in leukemia patients—a study in Chinese patients. Eur J Haematol, 79, 138–145.
8.
GiorginiA., and NobleA. (2007). Blockade of chronic graft-versus-host disease by alloantigen-induced CD4+CD25+Foxp3+regulatory T cells in nonlymphopenic hosts. J Leukoc Biol, 82, 1053–1061.
9.
HoffmannP., ErmannJ., and EdingerM. (2005). CD4+CD25+regulatory T cells in hematopoietic stem cell transplantation. Curr Top Microbiol Immunol, 293, 265–285.
10.
KapurR., EbelingS., and HagenbeekA. (2008). B-cell involvement in chronic graft-versus-host disease. Haematologica, 93, 1702–1711.
11.
LiY., ChenS., YangL., YinQ., GengS., WuX., et al. (2007). TRAV and TRBV repertoire, clonality and the proliferative history of umbilical cord blood T-cells. Transpl Immunol, 18, 151–158.
12.
LiY., LinC., and SchmidtC.A. (2012). New insights into antigen specific immunotherapy for chronic myeloid leukemia. Cancer Cell Int, 12, 52.
13.
LiuH., ZhaiX., SongZ., SunJ., XiaoY., NieD., et al. (2013). Busulfan plus fludarabine as a myeloablative conditioning regimen compared with busulfan plus cyclophosphamide for acute myeloid leukemia in first complete remission undergoing allogeneic hematopoietic stem cell transplantation: a prospective and multicenter study. J Hematol Oncol, 6, 15.
14.
LvM., and HuangX.J. (2012). Allogeneic hematopoietic stem cell transplantation in China: where we are and where to go. J Hematol Oncol, 5, 10.
15.
MagenauJ.M., QinX., TawaraI., RogersC.E., KitkoC., SchloughM., et al. (2010). Frequency of CD4(+)CD25(hi)FOXP3(+) regulatory T cells has diagnostic and prognostic value as a biomarker for acute graft-versus-host-disease. Biol Blood Marrow Transplant, 16, 907–914.
16.
MatoA.R., MorgansA., and LugerS.M. (2008). Novel strategies for relapsed and refractory acute myeloid leukemia. Curr Opin Hematol, 15, 108–114.
17.
MeyerE.H., HsuA.R., LilientalJ., LohrA., FlorekM., ZehnderJ.L., et al. (2013). A distinct evolution of the T-cell repertoire categorizes treatment refractory gastrointestinal acute graft-versus-host disease. Blood, 121, 4955–4962.
18.
O'KeefeC.L., SobecksR.M., WlodarskiM., RodriguezA., BellK., KuczkowskiE., et al. (2004). Molecular TCR diagnostics can be used to identify shared clonotypes after allogeneic hematopoietic stem cell transplantation. Exp Hematol, 32, 1010–1022.
19.
OyekunleA.A., KrogerN., ZabelinaT., AyukF., SchiederH., RengesH., et al. (2006). Allogeneic stem-cell transplantation in patients with refractory acute leukemia: a long-term follow-up. Bone Marrow Transplant, 37, 45–50.
20.
RiegerK., LoddenkemperC., MaulJ., FietzT., WolffD., TerpeH., et al. (2006). Mucosal FOXP3+regulatory T cells are numerically deficient in acute and chronic GvHD. Blood, 107, 1717–1723.
21.
SabattiniE., BacciF., SagramosoC., and PileriS.A. (2010). WHO classification of tumours of haematopoietic and lymphoid tissues in 2008: an overview. Pathologica, 102, 83–87.
22.
SchneiderM., MunderM., KarakhanovaS., HoA.D., and GoernerM. (2006). The initial phase of graft-versus-host disease is associated with a decrease of CD4+CD25+regulatory T cells in the peripheral blood of patients after allogeneic stem cell transplantation. Clin Lab Haematol, 28, 382–390.
23.
SempleK., YuY., WangD., AnasettiC., and YuX.Z. (2011). Efficient and selective prevention of GVHD by antigen-specific induced Tregs via linked-suppression in mice. Biol Blood Marrow Transplant, 17, 309–318.
24.
ThomasM.B., KollerC., YangY., ShenY., O'BrienS., KantarjianH., et al. (2003). Comparison of fludarabine-containing salvage chemotherapy regimens for relapsed/refractory acute myelogenous leukemia. Leukemia, 17, 990–993.
25.
TuovinenH., SalminenJ.T., and ArstilaT.P. (2006). Most human thymic and peripheral-blood CD4+CD25+regulatory T cells express 2 T-cell receptors. Blood, 108, 4063–4070.
26.
WuX., ZhuK., DuX., ChenS., YangL., WuJ., et al. (2011). Frequency analysis of TRBV subfamily sjTRECs to characterize T-cell reconstitution in acute leukemia patients after allogeneic hematopoietic stem cell transplantation. J Hematol Oncol, 4, 19.
27.
XuanL., HuangF., FanZ., ZhouH., ZhangX., YuG., et al. (2012a). Effects of intensified conditioning on Epstein-Barr virus and cytomegalovirus infections in allogeneic hematopoietic stem cell transplantation for hematological malignancies. J Hematol Oncol, 5, 46.
28.
XuanL., WuX., WuM., ZhangY., LiuH., FanZ., et al. (2012b). Effect of granulocyte colony-stimulating factor mobilization on the expression patterns, clonality and signal transduction of TRAV and TRBV repertoire. Immunobiology, 217, 816–822.
29.
ZhaiZ., SunZ., LiQ., ZhangA., LiuH., XuJ., et al. (2007). Correlation of the CD4+CD25high T-regulatory cells in recipients and their corresponding donors to acute GVHD. Transpl Int, 20, 440–446.
30.
ZhangX.L., LiY.Q., ChenS.H., YangL.J., ChenS., WuX.L., et al. (2009). The feature of clonal expansion of TCR Vbeta repertoire, thymic recent output function and TCRzeta chain expression in patients with immune thrombocytopenic purpura. Int J Lab Hematol, 31, 639–648.
