Monokine Induced by Interferon-γ (MIG/CXCL9) Is Derived from Both Donor and Recipient Sources during Rejection of Class II Major Histocompatibility Complex Disparate Skin Allografts

Auerbach, Michael B.; Shimoda, Naohiko; Amano, Hiroyuki; Rosenblum, Joshua M.; Kish, Danielle D.; Farber, Joshua M.; Fairchild, Robert L.

doi:10.2353/ajpath.2009.080516

Cited by 6 publications

(3 citation statements)

References 31 publications

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“…Interestingly, the recipients of WT hepatocytes had a significantly increased early production of CXCL9 (MIG) and CCL3 (MIP-1α) compared to those receiving CD47KO hepatocytes. These data are somewhat contradictory to previous studies showing that increased CXCL9 production is associated with enhanced alloresponses 22 23 24 . Although CCL3 might be upregulated during allograft rejection 24 , it was also reported to induce T cell apoptosis 25 .…”

Section: Discussioncontrasting

confidence: 99%

Donor CD47 controls T cell alloresponses and is required for tolerance induction following hepatocyte allotransplantation

Zhang

Wang

Tan

et al. 2016

Sci Rep

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CD47-deficient hepatocyte transplantation induces rapid innate immune cell activation and subsequent associated graft loss in syngeneic recipients. However, the role of donor CD47 in regulation of T-cell alloresponses is poorly understood. We addressed this question by assessing OVA-specific immune responses in mice following hepatocyte transplantation from CD47-competent or -deficient OVA-transgenic donors. Compared to sham-operated controls, intrasplenic transplantation of CD47-deficient OVA+ hepatocytes significantly accelerated rejection of OVA+ skin grafted 7 days after hepatocyte transplantation. In contrast, mice receiving CD47-competent OVA+ hepatocytes showed prolonged and even indefinite survival of OVA+ skin allografts. T cells from mice receiving CD47-deficient, but not CD47-competent, OVA+ hepatocytes showed significantly enhanced responses to OVA+ stimulators compared to sham-operated controls. In contrast to the production of tolerogenic cytokines (IL-4 and IL-10) in the recipients of CD47-competent hepatocytes, mice receiving CD47-deficient hepatocytes showed elevated production of IFN-γ and IL-1α. Moreover, significant expansion of myeloid-derived suppressor cells was detected in the recipients of CD47-competent hepatocytes, which was required for tolerance induction in these mice. Thus, donor CD47 plays an important role in the control of T-cell alloresponses and tolerance induction following hepatocyte transplantation. Our data also suggest that intrasplenic hepatocyte transplantation may provide a means to induce allograft tolerance.

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Section: Discussioncontrasting

confidence: 99%

Donor CD47 controls T cell alloresponses and is required for tolerance induction following hepatocyte allotransplantation

Zhang

Wang

Tan

et al. 2016

Sci Rep

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“…Second, IFN-γ plays an indispensable role in this particular transplant setting by up-regulating the expression of the single MHC class II alloantigen on donor keratinocytes [16]. Finally, CXCL9 and CXCL10, two chemokines induced by IFN-γ are required for tissue damages in this allogeneic combination [17].…”

Section: Discussionmentioning

confidence: 99%

IL-17A and IL-2-Expanded Regulatory T Cells Cooperate to Inhibit Th1-Mediated Rejection of MHC II Disparate Skin Grafts

et al. 2013

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Several evidences suggest that regulatory T cells (Treg) promote Th17 differentiation. Based on this hypothesis, we tested the effect of IL-17A neutralization in a model of skin transplantation in which long-term graft survival depends on a strong in vivo Treg expansion induced by transient exogenous IL-2 administration. As expected, IL-2 supplementation prevented rejection of MHC class II disparate skin allografts but, surprisingly, not in IL-17A-deficient recipients. We attested that IL-17A was not required for IL-2-mediated Treg expansion, intragraft recruitment or suppressive capacities. Instead, IL-17A prevented allograft rejection by inhibiting Th1 alloreactivity independently of Tregs. Indeed, T-bet expression of naive alloreactive CD4+ T cells and the subsequent Th1 immune response was significantly enhanced in IL-17A deficient mice. Our results illustrate for the first time a protective role of IL-17A in CD4+-mediated allograft rejection process.

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“…However, the elevated expression of the CXCR3‐binding chemokines in clinical acute rejection samples and the results of studies in murine models of transplantation in which this chemokine axis was genetically manipulated, would suggest that CXCR3 and its ligands are involved in recruiting effector T cells to the graft parenchyma [28,37,47–49]. Furthermore, a recent study demonstrated that CXCL9 from both donor and recipient sources would act in synergy during rejection of class II major histocompatibility complex disparate skin allografts [50].…”

Section: Discussionmentioning

confidence: 99%

High pretransplant serum levels of CXCL9 are associated with increased risk of acute rejection and graft failure in kidney graft recipients

Rotondi

Netti

Lazzeri

et al. 2009

Transplant International

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Summary Several clinical and experimental models have underlined the role of the CXCR3‐binding chemokines in the immune‐mediated kidney diseases. This study aimed to investigate the predictive value of measuring pretransplant CXCL9 levels for acute rejection (AR) onset and kidney transplantation outcome. Pretransplantation serum levels of CXCL9 were tested retrospectively in 252 kidney graft recipients, whose stratification in two groups according to CXCL9 levels (<272.1 pg/ml vs. >272.1 pg/ml) showed highly significant differences in 5‐year survival rates (97.7% vs. 73.3%; P < 0.001). Multivariate analysis demonstrated that among the analysed variables, CXCL9 [relative risk (RR) 11.708] and AR (RR 3.604) had the highest predictive power of graft loss. Accordingly, patients with AR (254.4 ± 22.1; P < 0.05) and, even more, those with anti‐thymoglobulin (ATG)‐treated AR also showed increased pretransplant serum CXCL9 levels (319.3 ± 28.1, P < 0.001). Moreover, CXCL9 expression and distribution were investigated in tissue specimens obtained from 10 patients affected by AR, and wide CXCL9 expression was detected not only in infiltrating inflammatory cells but also in vascular and tubular structures. Measurement of pretransplant serum CXCL9 levels might represent the tracking of a clinically useful parameter to identify subjects at high risk of AR and graft failure. These findings might be used for the individualization of immunosuppressive therapies.

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Monokine Induced by Interferon-γ (MIG/CXCL9) Is Derived from Both Donor and Recipient Sources during Rejection of Class II Major Histocompatibility Complex Disparate Skin Allografts

Cited by 6 publications

References 31 publications

Donor CD47 controls T cell alloresponses and is required for tolerance induction following hepatocyte allotransplantation

Donor CD47 controls T cell alloresponses and is required for tolerance induction following hepatocyte allotransplantation

IL-17A and IL-2-Expanded Regulatory T Cells Cooperate to Inhibit Th1-Mediated Rejection of MHC II Disparate Skin Grafts

High pretransplant serum levels of CXCL9 are associated with increased risk of acute rejection and graft failure in kidney graft recipients

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