Granulocyte colony-stimulating factor affects the distribution and clonality of TRGV and TRDV repertoire of T cells and graft-versus-host disease

Journal of Translational Medicine - Tập 9 Số 1 - 2011
Li Xuan1, Xiuli Wu1, Yu Zhang1, Fan Zhang1, Yiwen Ling1, Fen Huang1, Fuhua Zhang1, Xiao Zhai1, Qifa Liu1
1Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China

Tóm tắt

AbstractBackground

The immune modulatory effect of granulocyte colony-stimulating factor (G-CSF) on T cells resulted in an unexpected low incidence of graft-versus-host disease (GVHD) in allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Recent data indicated that gamma delta+T cells might participate in mediating graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect after allogeneic hematopoietic stem cell transplantation. However, whether G-CSF could influence the T cell receptors (TCR) of gamma delta+T cells (TRGVandTRDVrepertoire) remains unclear. To further characterize this feature, we compared the distribution and clonality ofTRGVandTRDVrepertoire of T cells before and after G-CSF mobilization and investigated the association between the changes of TCR repertoire and GVHD in patients undergoing G-CSF mobilized allo-PBSCT.

Methods

The complementarity-determining region 3 (CDR3) sizes of threeTRGVand eightTRDVsubfamily genes were analyzed in peripheral blood mononuclear cells (PBMCs) from 20 donors before and after G-CSF mobilization, using RT-PCR and genescan technique. To determine the expression levels ofTRGVsubfamily genes, we performed quantitative analysis ofTRGVI~III subfamilies by real-time PCR.

Results

The expression levels of threeTRGVsubfamilies were significantly decreased after G-CSF mobilization (P= 0.015, 0.009 and 0.006, respectively). The pattern ofTRGVsubfamily expression levels wasTRGVII >TRGVI >TRGVIII before mobilization, and changed toTRGVI >TRGVII >TRGVIII after G-CSF mobilization. The expression frequencies ofTRGVandTRDVsubfamilies changed at different levels after G-CSF mobilization. MostTRGVandTRDVsubfamilies revealed polyclonality from pre-G-CSF-mobilized and G-CSF-mobilized samples. Oligoclonality was detected inTRGVandTRDVsubfamilies in 3 donors before mobilization and in another 4 donors after G-CSF mobilization, distributed inTRGVII,TRDV1,TRDV3 andTRDV6, respectively. Significant positive association was observed between the invariable clonality ofTRDV1 gene repertoire after G-CSF mobilization and low incidence of GVHD in recipients (P= 0.015,OR= 0.047).

Conclusions

G-CSF mobilization not only influences the distribution and expression levels ofTRGVandTRDVrepertoire, but also changes the clonality of gamma delta+T cells. This alteration ofTRGVandTRDVrepertoire might play a role in mediating GVHD in G-CSF mobilized allo-PBSCT.

Từ khóa


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Journal of Translational Medicine

Tập 9 Số 1

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