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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

Serum concentrations of (A) CXCL9, (B) CXCL10, (C) IFN-γ, (D) IL-2, (E) IL-10 and (F) TGF-β in the recipient mice were determined by ELISA on day three following cardiac transplantation. **P<0.01; ***P<0.001; CXCL, C-X-C motif chemokine ligand; ELISA, enzyme-linked immunosorbent assay; IFN, interferon; IL, interleukin; TGF, transforming growth factor.
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f4-etm-08-01-0237: Serum concentrations of (A) CXCL9, (B) CXCL10, (C) IFN-γ, (D) IL-2, (E) IL-10 and (F) TGF-β in the recipient mice were determined by ELISA on day three following cardiac transplantation. **P<0.01; ***P<0.001; CXCL, C-X-C motif chemokine ligand; ELISA, enzyme-linked immunosorbent assay; IFN, interferon; IL, interleukin; TGF, transforming growth factor.

Mentions: ELISA was performed using sera obtained from the recipient mice at day three following cardiac transplantation. As shown in Fig. 4, statistically significant differences were observed in the cytokine expression levels between the groups (blank vs. control; control vs. experimental; skin graft vs. experimental). Furthermore, the expression levels of CXCL9 and CXCL10 in the serum were shown to correlate with the development of acute rejection. In addition, in the experimental group, the serum concentrations of IFN-γ and IL-2 were higher, while the concentrations of TGF-β and IL-10 were lower when compared with the control group. These observations indicated that the retransplantation model was more prone to the development of acute rejection compared with the transplantation model.


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)

Serum concentrations of (A) CXCL9, (B) CXCL10, (C) IFN-γ, (D) IL-2, (E) IL-10 and (F) TGF-β in the recipient mice were determined by ELISA on day three following cardiac transplantation. **P<0.01; ***P<0.001; CXCL, C-X-C motif chemokine ligand; ELISA, enzyme-linked immunosorbent assay; IFN, interferon; IL, interleukin; TGF, transforming growth factor.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4-etm-08-01-0237: Serum concentrations of (A) CXCL9, (B) CXCL10, (C) IFN-γ, (D) IL-2, (E) IL-10 and (F) TGF-β in the recipient mice were determined by ELISA on day three following cardiac transplantation. **P<0.01; ***P<0.001; CXCL, C-X-C motif chemokine ligand; ELISA, enzyme-linked immunosorbent assay; IFN, interferon; IL, interleukin; TGF, transforming growth factor.
Mentions: ELISA was performed using sera obtained from the recipient mice at day three following cardiac transplantation. As shown in Fig. 4, statistically significant differences were observed in the cytokine expression levels between the groups (blank vs. control; control vs. experimental; skin graft vs. experimental). Furthermore, the expression levels of CXCL9 and CXCL10 in the serum were shown to correlate with the development of acute rejection. In addition, in the experimental group, the serum concentrations of IFN-γ and IL-2 were higher, while the concentrations of TGF-β and IL-10 were lower when compared with the control group. These observations indicated that the retransplantation model was more prone to the development of acute rejection compared with the transplantation model.

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