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CXCL9 and CXCL10 accelerate acute transplant rejection mediated by alloreactive memory T cells in a mouse retransplantation model.

Zhuang J, Shan Z, Ma T, Li C, Qiu S, Zhou X, Lin L, Qi Z - Exp Ther Med (2014)

Bottom Line: The mean graft survival time of the heterotopic heart transplantations was 7.7 days in the experimental group (n=6), as compared with 3.25 days in the control group (n=6; P<0.001).In addition, gene expression and serum concentrations of CXCL9, CXCL10, interferon-γ, and interleukin-2 were markedly higher in the experimental group when compared with the control group.Thus, the observations enhance the understanding of the mechanism underlying the increased expression and secretion of CXCL9 and CXCL10 by alloreactive memory T cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiac Surgery, The First Affiliated Hospital, Xiamen University, Xiamen, Fujian 361003, P.R. China.

ABSTRACT
C-X-C motif chemokine ligand (CXCL) 9 and CXCL10 play key roles in the initiation and development of acute transplant rejection. Previously, higher levels of RANTES expression and secretion were demonstrated in retransplantation or T-cell memory-transfer models. In the present study, the effect of the chemokines, CXCL9 and CXCL10, were investigated in a mouse retransplantation model. BALB/c mice were used as donors, while C57BL/6 mice were used as recipients. In the experimental groups, a heterotopic heart transplantation was performed six weeks following skin grafting. In the control groups, a heterotopic heart transplantation was performed without skin grafting. Untreated mice served as blank controls. The mean graft survival time of the heterotopic heart transplantations was 7.7 days in the experimental group (n=6), as compared with 3.25 days in the control group (n=6; P<0.001). On day three following cardiac transplantation, histological evaluation of the grafts revealed a higher International Society for Heart & Lung Transplantation grade in the experimental group as compared with the control group. In addition, gene expression and serum concentrations of CXCL9, CXCL10, interferon-γ, and interleukin-2 were markedly higher in the experimental group when compared with the control group. Differences between the levels of CXCL9 and CXCL10 in the pre- and post-transplant mice indicated that the chemokines may serve as possible biomarkers to predict acute rejection. The results of the present study demonstrated that CXCL9 and CXCL10 play a critical role in transplantation and retransplantation. High levels of these cytokines during the pre-transplant period may lead to extensive acute rejection. Thus, the observations enhance the understanding of the mechanism underlying the increased expression and secretion of CXCL9 and CXCL10 by alloreactive memory T cells.

No MeSH data available.


Related in: MedlinePlus

Relative gene expression levels of (A) CXCL9, (B) CXCL10, (C) IFN-γ, (D) IL-2, (E) IL-10 and (F) TGF-β in the cardiac allografts of the recipient mice. *P<0.05; **P<0.01; ***P<0.001; IFN, interferon; IL, interleukin; TGF, transforming growth factor; CXCL, C-X-C motif chemokine ligand.
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f3-etm-08-01-0237: Relative gene expression levels of (A) CXCL9, (B) CXCL10, (C) IFN-γ, (D) IL-2, (E) IL-10 and (F) TGF-β in the cardiac allografts of the recipient mice. *P<0.05; **P<0.01; ***P<0.001; IFN, interferon; IL, interleukin; TGF, transforming growth factor; CXCL, C-X-C motif chemokine ligand.

Mentions: RNA was isolated from the cardiac grafts on day three following the transplantation in recipient mice, and the cDNA products were synthesized and analyzed by qPCR. As shown in Fig. 3, statistically significant differences with regard to cytokine gene expression were observed among the groups (blank vs. control; control vs. experimental; skin graft vs. experimental). As shown in Fig. 3, the relative gene expression levels of IFN-γ and IL-2 were higher in the experimental group than in the control group, whereas the relative gene expression levels of IL-10 and TGF-β were lower in the experimental group compared with the control group.


CXCL9 and CXCL10 accelerate acute transplant rejection mediated by alloreactive memory T cells in a mouse retransplantation model.

Zhuang J, Shan Z, Ma T, Li C, Qiu S, Zhou X, Lin L, Qi Z - Exp Ther Med (2014)

Relative gene expression levels of (A) CXCL9, (B) CXCL10, (C) IFN-γ, (D) IL-2, (E) IL-10 and (F) TGF-β in the cardiac allografts of the recipient mice. *P<0.05; **P<0.01; ***P<0.001; IFN, interferon; IL, interleukin; TGF, transforming growth factor; CXCL, C-X-C motif chemokine ligand.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061216&req=5

f3-etm-08-01-0237: Relative gene expression levels of (A) CXCL9, (B) CXCL10, (C) IFN-γ, (D) IL-2, (E) IL-10 and (F) TGF-β in the cardiac allografts of the recipient mice. *P<0.05; **P<0.01; ***P<0.001; IFN, interferon; IL, interleukin; TGF, transforming growth factor; CXCL, C-X-C motif chemokine ligand.
Mentions: RNA was isolated from the cardiac grafts on day three following the transplantation in recipient mice, and the cDNA products were synthesized and analyzed by qPCR. As shown in Fig. 3, statistically significant differences with regard to cytokine gene expression were observed among the groups (blank vs. control; control vs. experimental; skin graft vs. experimental). As shown in Fig. 3, the relative gene expression levels of IFN-γ and IL-2 were higher in the experimental group than in the control group, whereas the relative gene expression levels of IL-10 and TGF-β were lower in the experimental group compared with the control group.

Bottom Line: The mean graft survival time of the heterotopic heart transplantations was 7.7 days in the experimental group (n=6), as compared with 3.25 days in the control group (n=6; P<0.001).In addition, gene expression and serum concentrations of CXCL9, CXCL10, interferon-γ, and interleukin-2 were markedly higher in the experimental group when compared with the control group.Thus, the observations enhance the understanding of the mechanism underlying the increased expression and secretion of CXCL9 and CXCL10 by alloreactive memory T cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiac Surgery, The First Affiliated Hospital, Xiamen University, Xiamen, Fujian 361003, P.R. China.

ABSTRACT
C-X-C motif chemokine ligand (CXCL) 9 and CXCL10 play key roles in the initiation and development of acute transplant rejection. Previously, higher levels of RANTES expression and secretion were demonstrated in retransplantation or T-cell memory-transfer models. In the present study, the effect of the chemokines, CXCL9 and CXCL10, were investigated in a mouse retransplantation model. BALB/c mice were used as donors, while C57BL/6 mice were used as recipients. In the experimental groups, a heterotopic heart transplantation was performed six weeks following skin grafting. In the control groups, a heterotopic heart transplantation was performed without skin grafting. Untreated mice served as blank controls. The mean graft survival time of the heterotopic heart transplantations was 7.7 days in the experimental group (n=6), as compared with 3.25 days in the control group (n=6; P<0.001). On day three following cardiac transplantation, histological evaluation of the grafts revealed a higher International Society for Heart & Lung Transplantation grade in the experimental group as compared with the control group. In addition, gene expression and serum concentrations of CXCL9, CXCL10, interferon-γ, and interleukin-2 were markedly higher in the experimental group when compared with the control group. Differences between the levels of CXCL9 and CXCL10 in the pre- and post-transplant mice indicated that the chemokines may serve as possible biomarkers to predict acute rejection. The results of the present study demonstrated that CXCL9 and CXCL10 play a critical role in transplantation and retransplantation. High levels of these cytokines during the pre-transplant period may lead to extensive acute rejection. Thus, the observations enhance the understanding of the mechanism underlying the increased expression and secretion of CXCL9 and CXCL10 by alloreactive memory T cells.

No MeSH data available.


Related in: MedlinePlus