Tim-3 expression in human kidney allografts

Ponciano, Viviane Campos; Renesto, Paulo Guilherme; Nogueira, Eliana; Rangel, Érika Bevilaqua; Cenedeze, Marcos Antônio; Franco, Marcello; Câmara, Niels Olsen Saraiva; Pacheco-Silva, Álvaro

doi:10.1016/j.trim.2006.11.003

Cited by 21 publications

(12 citation statements)

References 22 publications

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“…Tim-3, a regulatory molecule expressed on the surface of Th1 lymphocytes, was detected in urine [16] and kidney allograft nephrectomy samples [17] during an acute rejection episode. Furthermore, in an experimental model, Tim-3 blockage resulted in abrogation of tolerance induction by costimulation blockage [18].…”

Section: Discussionmentioning

confidence: 99%

Detection of the Tim-3 ligand, galectin-9, inside the allograft during a rejection episode

Naka

Ponciano

Cenedeze

et al. 2009

International Immunopharmacology

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Section: Discussionmentioning

confidence: 99%

Detection of the Tim-3 ligand, galectin-9, inside the allograft during a rejection episode

Naka

Ponciano

Cenedeze

et al. 2009

International Immunopharmacology

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“…Small studies indicate that TIM-3 mRNA levels are significantly higher within rejecting allografts and that there is a strong correlation between intra-graft TIM-3 and IFN-γ levels. Interestingly, treatment-refractory rejection episodes showed relatively lower levels of TIM-3, suggesting a link between lack of negative costimulatory signaling and poorer allograft outcomes (Ponciano et al, 2007). In addition, measurement of TIM-3 mRNA in urine and blood have proved accurate in the differentiation of delayed graft function (DGF) with acute tubular necrosis versus DGF with acute rejection (Manfro et al, 2008).…”

Section: Tim-3:galectin-9mentioning

confidence: 99%

The Role of Coinhibitory Signaling Pathways in Transplantation and Tolerance

McGrath¹,

Najafian²

2012

Front. Immun.

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Negative costimulatory molecules, acting through so-called inhibitory pathways, play a crucial role in the control of T cell responses. This negative “second signal” opposes T cell receptor activation and leads to downregulation of T cell proliferation and promotes antigen specific tolerance. Much interest has focused upon these pathways in recent years as a method to control detrimental alloresponses and promote allograft tolerance. However, recent experimental data highlights the complexity of negative costimulatory pathways in alloimmunity. Varying effects are observed from molecules expressed on donor and recipient tissues and also depending upon the activation status of immune cells involved. There appears to be significant overlap and redundancy within these systems, rendering this a challenging area to understand and exploit therapeutically. In this article, we will review the literature at the current time regarding the major negative costimulation pathways including CTLA-4:B7, PD-1:PD-L1/PD-L2 and PD-L1:B7-1, B7-H3, B7-H4, HVEM:BTLA/CD160, and TIM-3:Galectin-9. We aim to outline the role of these pathways in alloimmunity and discuss their potential applications for tolerance induction in transplantation.

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“…Administration of the TIM-3 ligand galectin-9 resulted in significantly prolonged graft survival in both murine skin and cardiac transplant models (Cai et al, 2013; He et al, 2009), and was associated with a reduction in both Th1 and Th17 cell effector function and enhanced Treg cell suppressor function (Boenisch et al, 2010). Subsequent investigation in clinical transplantation revealed elevated TIM-3 mRNA levels in rejecting kidney grafts as compared to patients with stable graft function or patients with other causes of allograft dysfunction (Ponciano et al, 2007), raising the possibility that TIM-3 expression could be used as a biomarker to diagnose acute cellular rejection. While this idea may seem to contradict the finding that TIM-3 functions in a coinhibitory manner to limit T cell activation during transplantation, it is interesting to note that although TIM-3 levels were found to be increased in all cases of acute rejection, patients that were unresponsive to treatment possessed lower intra-graft levels of TIM-3, suggesting that strong TIM-3 signaling may help rescue graft function (Renesto et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

T Cell Cosignaling Molecules in Transplantation

Ford

2016

Immunity

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The ultimate outcome of alloreactivity vs. tolerance following transplantation is potently influenced by the constellation of cosignaling molecules expressed by immune cells during priming with alloantigen, and the net sum of costimulatory and coinhibitory signals transmitted via ligation of these molecules. Intense investigation over the last two decades has yielded a detailed understanding of the kinetics, cellular distribution, and intracellular signaling networks of cosignaling molecules such as the CD28, TNF and TIM families of receptors in alloimmunity. More recent work has better defined the cellular and molecular mechanisms by which engagement of cosignaling networks serve to either dampen or augment alloimmunity. These findings will likely aid in the rational development of novel immunomodulatory strategies to prolong graft survival and improve outcomes following transplantation.

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Tim-3 expression in human kidney allografts

Cited by 21 publications

References 22 publications

Detection of the Tim-3 ligand, galectin-9, inside the allograft during a rejection episode

Detection of the Tim-3 ligand, galectin-9, inside the allograft during a rejection episode

The Role of Coinhibitory Signaling Pathways in Transplantation and Tolerance

T Cell Cosignaling Molecules in Transplantation

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