CXC Chemokine Ligand (CXCL) 9 and CXCL10 Are Antagonistic Costimulation Molecules during the Priming of Alloreactive T Cell Effectors

Rosenblum, Joshua M.; Shimoda, Naohiko; Schenk, Austin D.; Zhang, Howard; Kish, Danielle D.; Keslar, Karen; Farber, Joshua M.; Fairchild, Robert L.

doi:10.4049/jimmunol.0903831

Cited by 67 publications

(64 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to the role of CXCL9/ CXCL10 in the recruitment of T cells to the allograft, Rosenblum et al (2010) recently showed that these chemokines regulate donor-specific CD8 þ T-cell priming. As such, in a murine model of cardiac transplantation using KO mice for either the CXCL9 or CXCL10 gene, CXCL9 promoted, whereas CXCL10 inhibited the differentiation of IFN-g-producing donor-specific CD8 þ T cells.…”

Section: Chemokinesmentioning

confidence: 99%

Effector Mechanisms of Rejection

Moreau

Varey

Anegón

et al. 2013

Cold Spring Harbor Perspectives in Medicine

145

136

View full text Add to dashboard Cite

Section: Chemokinesmentioning

confidence: 99%

Effector Mechanisms of Rejection

Moreau

Varey

Anegón

et al. 2013

Cold Spring Harbor Perspectives in Medicine

145

136

View full text Add to dashboard Cite

“…Chemokine (C-X-C motif) ligand 10 (CXCL10) as a major chemokine, as well as the absence of acid-leucine-arginine peptide chemokine, detected in an allograft and isograft model, was found to accelerate acute allograft rejection after organ transplantation (9-11); this occurred via binding to the G-protein-coupled receptor CXCL receptor 3 (CXCR3), which was expressed in multiple cells such as primed effector T cells producing interferon (IFN)-γ and Tm cells (11,12). CXCL10 has been demonstrated to have an important role in the generation of T lymphocyte effector functions in infection and first transplants (13); however, few, if any, experimental and clinical studies on the role of CXCL10 in accelerated rejection mediated by Tm cells are available.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of C‑X‑C motif chemokine 10 reduces graft loss mediated by memory CD8+ T cells in a rat cardiac re‑transplant model

Deng

et al. 2017

Exp Ther Med

View full text Add to dashboard Cite

Abstract. The interaction of chemokine (C-X-C motif) ligand 10 (CXCL10) with its receptor (CXCR3) is a critical process in recruiting donor reactive T cells to a graft and alloantigen-specific memory T (Tm) cells exert a principal function in promoting graft dysfunction during accelerated cardiac rejection. However, whether CXCL10 chemokine exerts any effects on acute accelerated rejection mediated by CD8 + Tm cells in a re-transplant model has remained elusive. The present study established a cardiac transplant model by advanced microsurgery technology and improved organ storage. A novel rat model of cardiac re-transplantation was established at 40 days following primary heart transplant. The experiment included two parts, and when models were established, the rats were divided into two groups: Primary cardiac transplant (HTx) and re-transplantation without treatment (HRTx). In part 1, recipients from part 2, including re-transplantation without treatment (HRTx+NS) and re-transplantation treated with anti-CXCL10 antibodies (500 µg every other day by intraperitoneal injection; HRTx+CXCL10 Abs group). The graft survival time was observed and graft infiltration by inflammatory cells was assessed via histology of cardiac graft sections; in addition, the gene expression and the serum concentration of CXCL10 in each group was assessed. Indexes such as rejection-associated cytokines were assayed by reverse-transcription quantitative PCR and ELISA kits, and flow cytometry of splenocytes was used to detect Tm cells in the re-transplantation groups. The results demonstrated that level of CXCL10 was significantly increased and the graft mean survival time was shortened accompanied with aggravated lymphocyte cell infiltration in the HRTx group when compared that in the HTx group; in addition, the serum levels and mRNA expression of interleukin (IL)-2 and interferon (IFN)-γ were increased, while transforming growth factor (TGF)-β was decreased in the HRTx group. Furthermore, neutralization of CXCL10 prolonged the graft mean survival time and delayed accelerated rejection. Compared with that in the HRTx+NS group, serum levels and graft tissue mRNA expression of IFN-γ and IL-2 were decreased in the HRTx+CXCL10 Abs group, while TGF-β mRNA was significantly increased but the serum concentration was not significantly affected. In addition, there was no difference in IL-10 between the two groups, while delayed accelerated rejection paralleled with inflammatory cell infiltration decreased and the proliferation and differentiation of CD8 + Tm cells in secondary lymphoid organs were reduced in the HRTx+CXCL10 Abs group vs. those in the HRTx+NS group. The present study demonstrated that CXCL10 had a crucial role in cardiac transplantation and re-transplantation, and that treatment with CXCL10 antibodies delays accelerated acute rejection mediated by Tm cells in a rat model of cardiac re-transplantation. IntroductionA multidisciplinary program has been initiated to better establish transplantation for prolonging survival time of cardi...

show abstract

“…Moreover, the expression pattern of these chemokines in tissues during inflammation is different (36)(37)(38). Recent studies in a murine cardiac allograft model demonstrated antagonistic effects of Mig and IP-10 on the costimulation of alloreactive IFN-gproducing CD8 T cells (39), and we recently observed differential effects of these two chemokines on the activation of tumorspecific T cells as well (A. Gorbachev, manuscript in preparation).…”

Section: Discussionmentioning

confidence: 95%

Cutaneous Tumors Cease CXCL9/Mig Production as a Result of IFN-γ–Mediated Immunoediting

Petro

Kish

Guryanova

et al. 2013

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

During growth in the host, tumor cells are subjected to the stresses of innate and adaptive immunity (immunoediting), which provoke epigenetic changes in the tumor and increase tumor resistance to these immune responses. Our recent studies in methylcholanthrene-induced fibrosarcomas have indicated the appearance and rapid growth of tumor variants deficient in producing the T cell chemoattractant chemokine CXCL9/Mig, an important component of antitumor immunity. In the current report, we demonstrate that highly tumorigenic Mig-deficient tumor variants arise in both cutaneous fibrosarcoma and melanoma as a result of immune stress imposed by IFN-γ and T cells. The consequence of the loss of tumor-derived Mig expression is the increased resistance of Mig-deficient tumors to T cell-mediated immunity, which promotes the accelerated growth of these tumor variants. Remarkably, the ability of Mig-deficient tumor cells to express another CXCR3 ligand, CXCL10/IFN-γ–inducible protein, does not compensate for the absent antitumor functions of Mig, suggesting a nonredundant role for this chemokine in the suppression of tumor growth. To our knowledge, these studies report for the first time that IFN-γ–mediated stress leads to the loss of specific chemokine expression by tumor cells, which in turn promotes tumor growth and evasion of the immune response.

show abstract

CXC Chemokine Ligand (CXCL) 9 and CXCL10 Are Antagonistic Costimulation Molecules during the Priming of Alloreactive T Cell Effectors

Cited by 67 publications

References 56 publications

Effector Mechanisms of Rejection

Effector Mechanisms of Rejection

Inhibition of C‑X‑C motif chemokine 10 reduces graft loss mediated by memory CD8+ T cells in a rat cardiac re‑transplant model

Cutaneous Tumors Cease CXCL9/Mig Production as a Result of IFN-γ–Mediated Immunoediting

Contact Info

Product

Resources

About