T cell costimulation by chemokine receptors

Molon, Barbara; Gri, Giorgia; Bettella, Monica; Gómez‐Moutón, Concepción; Lanzavecchia, Antonio; Martı́nez-A, Carlos; Mañes, Santos; Viola, Antonella

doi:10.1038/ni1191

Cited by 302 publications

(339 citation statements)

References 46 publications

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“…17 Our previous study has documented that the presence of the 32-bp deletion within the CCR5 gene associates with a lower risk of acute GvHD after allogeneic HSCT in humans, 18 suggesting that the deletion within the chemokine receptor can affect cell trafficking by decreased interaction with its ligands. 19 Taking into account that viral reactivations may promote GvHD, 20 it could also be assumed that the expression of functional CCR5 may influence the initiation/perpetuation of GvHD by promotion of viral reactivation.…”

Section: Discussionmentioning

confidence: 99%

The presence of functional CCR5 and EBV reactivation after allogeneic haematopoietic stem cell transplantation

Bogunia‐Kubik

Jaskuła

Lange

2007

Bone Marrow Transplant

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EBV reactivation is a serious complication affecting the recipients of allogeneic haematopoietic stem cell transplants (allogeneic HSCT). Recent reports have suggested that EBV reactivation induces increased expression of C-C chemokine receptor-5 (CCR5) or its ligands. Therefore, the 32-nucleotide deletion within the CCR5-encoding gene (CCR5D32 polymorphism) was analysed in 92 recipients of allogeneic HSCT and their donors and related with EBV load. In addition in 30 patients, at the same time points employing a real-time PCR technique, the number of viral copies and CCR5 transcripts were assessed. The incidence of EBV reactivation 2-3 months after transplantation was significantly lower in patients carrying the CCR5D32 allele (P ¼ 0.008). The association was confirmed in multivariate analysis, in which recipient CCR5D32 (OR ¼ 0.166, P ¼ 0.026) in addition to recipient age (OR ¼ 1.536, P ¼ 0.034) were identified as independent risk factors for EBV reactivation. Moreover, EBV reactivation was more frequently seen when patients and their donors were lacking the CCR5 deletion mutation as compared to other donor-recipient pairs (P ¼ 0.022). The CCR5 expression was significantly higher in the group of patients having EBV reactivation than in those lacking it (R ¼ 25.354, P ¼ 0.024). These results suggest that the expression of functional CCR5 plays a role in initiation/perpetuation of EBV reactivation.

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Section: Discussionmentioning

confidence: 99%

The presence of functional CCR5 and EBV reactivation after allogeneic haematopoietic stem cell transplantation

Bogunia‐Kubik

Jaskuła

Lange

2007

Bone Marrow Transplant

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“…In the case of proinflammatory effector T cells, CCR5 alters the length of their interaction with antigen-presenting cells, leading to enhanced T cell activation (43). To assess whether CCR5 is required for the suppressive activity of T R cells, we performed coculturing experiments with CD25 ϩ cells prepared from either wild-type mice or CCR5 Ϫ/Ϫ gene deletion mutants.…”

Section: D)mentioning

confidence: 99%

Alloantigen-enhanced accumulation of CCR5⁺‘effector’ regulatory T cells in the gravid uterus

Kallikourdis

Andersen

Welch

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

130

114

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Regulatory T cells play an essential role in preventing fetal rejection by the maternal immune system. Here we show that, based on the expression of CCR5, regulatory T cells can be divided into a highly suppressive CCR5 ؉ and a far less suppressive CCR5 ؊ subpopulation, suggesting that the former represent the effector arm of regulatory T cells. Although regulatory T cells from CCR5 ؊/؊ gene deletion mutants still suppress, they are less effective mediators of maternal-fetal tolerance. The accumulation of CCR5 ؉ regulatory T cells at this site appears to be enhanced by alloantigen. This finding is in stark contrast to the systemic expansion of regulatory T cells during pregnancy, which appears to be alloantigenindependent. The fact that CCR5 ؉ regulatory T cells preferentially accumulate in the gravid uterus and that expression of CCR5 on regulatory T cells can be induced by activation lead us to propose that CCR5 is responsible for the accumulation of those regulatory T cells that have been activated by paternal antigens.effector T cells ͉ pregnancy ͉ tolerance ͉ chemokine receptor R egulatory T cells (T R cells) play an important role in the maintenance of peripheral tolerance and the prevention of autoimmunity (1). Where T R cells exert their suppressive function and what attracts them to and retains them at their site of action is poorly understood. Inducible T R cells (Tr1-like cells) have a preference for skin homing (2), whereas naturally occurring Foxp3 ϩ T R cells can be found in all lymphoid organs (3, 4). The CD103 ϩ subpopulation of T R cells has been shown to home to the site of inflammation (5); however, the mechanism by which this occurs remains elusive.Previously, we have demonstrated that naturally occurring T R cells mediate maternal tolerance to the fetus and can be found in the uterus during pregnancy (6). Although the uterine accumulation of macrophages (7), natural killer cells (8, 9), and eosinophils (10) has been extensively studied, there has been no insight on how T R cells find their way to the gravid uterus.Upon activation, professional antigen-presenting cells express the chemokine CCL4, which leads to the recruitment and/or retention of T R cells (11). Although it remains unclear which chemokine receptor is responsible for the CCL4-mediated effects on T R cells, biochemical studies have shown CCL4 to bind to the chemokine receptor CCR5 (12). Expression of CCR5 on T cells has been associated with both proinflammatory and antiinflammatory T cell function in mouse and human. CCR5 is thought to be expressed on antigen-experienced, effector T cells that home toward sites of inflammation outside the secondary lymphoid organs (13-15). CCR5 ϩ T cells have been shown to infiltrate inflamed sites such as the synovium of rheumatoid arthritis patients (16,17) and the central nervous system of mice with experimental autoimmune encephalomyelitis (18). Expression of CCR5 in pancreatic islets correlates with increased severity of diabetes in mice (19), and CCR5 is thought to mediate T cell migratio...

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“…Dans cette optique, il a été suggéré que les antagonistes de CCR5 puissent être bénéfiques dans la prévention et le traitement des LEMP-SIRI [33,34]. CCR5 est un récepteur de chimiokines (principalement des C-C motif chemokines, CCL-3, -4 et -5) impliqué dans l'activation des lymphocytes T et leur migration vers les sites inflammatoires [35]. Les antagonistes de ce récepteur ont été initialement développés pour leurs propriétés antivirales permettant d'inhiber les interactions entre le VIH et CCR5, le principal corécepteur du virus.…”

Section: Resultsunclassified

Migration et pathogénicité des lymphocytes T CD8 dans les maladies du système nerveux central

2015

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T cell costimulation by chemokine receptors

Cited by 302 publications

References 46 publications

The presence of functional CCR5 and EBV reactivation after allogeneic haematopoietic stem cell transplantation

The presence of functional CCR5 and EBV reactivation after allogeneic haematopoietic stem cell transplantation

Alloantigen-enhanced accumulation of CCR5⁺‘effector’ regulatory T cells in the gravid uterus

Migration et pathogénicité des lymphocytes T CD8 dans les maladies du système nerveux central

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T cell costimulation by chemokine receptors

Cited by 302 publications

References 46 publications

The presence of functional CCR5 and EBV reactivation after allogeneic haematopoietic stem cell transplantation

The presence of functional CCR5 and EBV reactivation after allogeneic haematopoietic stem cell transplantation

Alloantigen-enhanced accumulation of CCR5+‘effector’ regulatory T cells in the gravid uterus

Migration et pathogénicité des lymphocytes T CD8 dans les maladies du système nerveux central

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Alloantigen-enhanced accumulation of CCR5⁺‘effector’ regulatory T cells in the gravid uterus