Development of a novel chemokine-mediated in vivo T cell recruitment assay

Campanella, Gabriele; Medoff, Benjamin D.; Manice, Lindsay A.; Luster, Andrew D.

doi:10.1016/j.jim.2007.12.002

Cited by 43 publications

(46 citation statements)

References 34 publications

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“…However, the CXCL11 gene in C57BL/6 mouse strain, from which NSG mouse was developed, contains a point mutation and a single-base deletion that results in a reading frame shift. Hence, a non-functional CXCL11 protein product is produced [24]; only CXCL9 and CXCL10 are probably the functional chemokines in this cluster to act on and to attract OT-I cell migration to the treated tumors. The data also revealed significant elevation of several additional chemokines.…”

Section: Resultsmentioning

confidence: 99%

An HSV-2 based oncolytic virus can function as an attractant to guide migration of adoptively transferred T cells to tumor sites

Rivera

Tao

et al. 2014

Oncotarget

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Adoptive T-cell therapy has shown promises for cancer treatment. However, for treating solid tumors, there is a need for improving the ability of the adoptively transferred T cells to home to tumor sites. We explored the possibility of using an oncolytic virus derived from HSV-2, which can actively pull T effector cells to the site of infection, as a local attractant for migration of adoptively transferred T cells. Our data show that intratumoral administration of this virus can indeed attract active migration of the adoptively transferred T cells to the treated tumor. Moreover, once attracted to the tumor site by the virus, T cells persisted in there significantly longer than in mock-treated tumor. Chemokine profiling identified significant elevation of CXCL9 and CXCL10, as well as several other chemokines belonging to the inflammatory chemokine family in the virus-treated tumors. These chemokines initially guided the T-cell migration to and then maintained their persistence in the tumor site, leading to a significantly enhanced therapeutic effect. Our data suggests that this virotherapy may be combined with adoptive T-cell therapy to potentiate its therapeutic effect against solid tumors that are otherwise difficult to manage with the treatment alone.

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Section: Resultsmentioning

confidence: 99%

An HSV-2 based oncolytic virus can function as an attractant to guide migration of adoptively transferred T cells to tumor sites

Rivera

Tao

et al. 2014

Oncotarget

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“…Chemokines and chemokine receptors guide the migration of effector cells into inflammatory sites, which are critical for the pathogenesis of autoimmune diseases [3, 4, 33, 34]. However, the observation in TGC3 mice that inflammatory cells accumulate within the inflammatory sites of liver in the absence of CXCR3 suggests that the pathogenic role of CXCR3 deficient CD8+ T cells does not require the chemotaxis of CXCR3 and is likely mediated either by other redundant chemokine(s) mediated chemotaxis or due to the absence of inhibitory signals normally provided by CXCR3 ligation.…”

Section: Discussionmentioning

confidence: 99%

“…CXCR3 is upregulated following CTL and Th1 cell differentiation [2]. CXCL9 (MIG), CXCL10 (IP-10), and CXCL11 are the natural ligands of CXCR3 [3–5]. CXCR3 is functionally pleiotropic; it plays an important role in the chemotaxis of Tregs to sites of inflammation following binding [6, 7], but also participates in T cell differentiation [5, 8].…”

Section: Introductionmentioning

confidence: 99%

Chemokine receptor CXCR3 deficiency exacerbates murine autoimmune cholangitis by promoting pathogenic CD8+ T cell activation

Wen

Liu

et al. 2017

Journal of Autoimmunity

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CXC Chemokine Receptor 3 (CXCR3) is functionally pleiotropic and not only plays an important role in chemotaxis, but also participates in T cell differentiation and may play a critical role in inducing and maintaining immune tolerance. These observations are particularly critical for autoimmune cholangitis in which CXCR3 positive T cells are found around the portal areas of both humans and mouse models of primary biliary cholangitis (PBC). Herein, we investigated the role of CXCR3 in the pathogenesis of autoimmune cholangitis. We have taken advantage of a unique CXCR3 knockout dnTGFβRII mouse to focus on the role of CXCR3, both by direct observation of its influence on the natural course of disease, as well as through adoptive transfer studies into Rag−/− mice. We report herein that not only do CXCR3 deficient mice develop an exacerbation of autoimmune cholangitis associated with an expanded effector memory T cell number, but also selective adoptive transfer of CXCR3 deficient CD8+ T cells induces autoimmune cholangitis. In addition, gene microarray analysis of CXCR3 deficient CD8+ T cells reveal an intense pro-inflammatory profile. Our data suggests that the altered gene profiles induced by CXCR3 deficiency promotes autoimmune cholangitis through pathogenic CD8+ T cells. These data have significance for human PBC and other autoimmune liver diseases in which therapeutic intervention might be directed to chemokines and/or their receptors.

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“…Previous efforts by us have shown that a direct intratracheal administration of mouse IP-10 into the lungs of C57BL/6 mice dose-responsively recruited exogenously and systemically administered ex vivo activated syngeneic OT-1 CD8þ T cells 48 h before the IP-10 challenge and that 5.0 mg of intratracheal IP-10 gave an good signal-to-noise-ratio [41]. Figure 3 shows that this IP-10 induced in vivo cell migration can be significantly and dose-responsively mitigated by systemic injection of the 20A9 mAb.…”

Section: Mab Clone 20a9 Antagonizes Ip-10 Induced Cell Migration In Vivomentioning

confidence: 98%

An antibody to IP-10 is a potent antagonist of cell migrationin vitroandin vivoand does not affect disease in several animal models of inflammation

et al. 2009

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IP-10 secretion is induced by pro-inflammatory cytokines and mediates the migration of CXCR3+ cells. Its elevation in clinical samples has been associated with multiple inflammatory diseases and its antagonism has been reported to be effective in several animal models of inflammatory disease. We generated a mouse anti-mouse IP-10 monoclonal antibody (mAb; Clone 20A9) that specifically bound murine IP-10 with high affinity and inhibited in vitro IP-10 induced BaF3/mCXCR3 cell migration with an IC(50) of approximately 4 nM. The 20A9 mAb was completely absorbed in vivo and had dose proportional pharmacokinetic exposure with a serum half life of 2.4-6 days. The 20A9 mAb inhibited IP-10 mediated T-cell recruitment to the airways, indicating that it is effective in vivo. However, administration of the 20A9 mAb had no significant effect on disease in mouse models of delayed type hypersensitivity, collagen induced arthritis, cardiac allograft transplantation tolerance, EAE or CD4+ CD45RBHi T-cell transfer-induced IBD. These data suggest that the 20A9 mAb can antagonize IP-10 mediated chemotaxis in vitro and in vivo and that this is insufficient to cause a therapeutic benefit in multiple mouse models of inflammatory disease.

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Development of a novel chemokine-mediated in vivo T cell recruitment assay

Cited by 43 publications

References 34 publications

An HSV-2 based oncolytic virus can function as an attractant to guide migration of adoptively transferred T cells to tumor sites

An HSV-2 based oncolytic virus can function as an attractant to guide migration of adoptively transferred T cells to tumor sites

Chemokine receptor CXCR3 deficiency exacerbates murine autoimmune cholangitis by promoting pathogenic CD8+ T cell activation

An antibody to IP-10 is a potent antagonist of cell migrationin vitroandin vivoand does not affect disease in several animal models of inflammation

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