An Agonistic Anti-BTLA mAb (3C10) Induced Generation of IL-10-Dependent Regulatory CD4+ T Cells and Prolongation of Murine Cardiac Allograft

Uchiyama, Masateru; Jin, Xiangyuan; Matsuda, Hironori; Bashuda, Hisashi; Imazuru, Tomohiro; Shimokawa, Tomoki; Yagita, Hideo; Niimi, Masanori

doi:10.1097/01.tp.0000438204.96723.8b

Cited by 35 publications

(34 citation statements)

References 43 publications

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“…This regulation was mediated by an IL-10-dependent mechanism of suppression. 53 The intervention with two antibodies against the HVEM/ BTLA pathway, including the anti-HVEM mAb (clone 6C9), which is capable of blocking BTLA/HVEM interactions but not HVEM/LIGHT interactions 20 and the anti-BTLA mAb (clone 4G12b, which is a non-depleting, agonist antibody capable of attenuating in vivo graft versus host disease), did not affect the allogeneic humoral immune response. 27,54 This result means that neither BTLA co-inhibition nor the HVEM/BTLA blockade influenced the course of the alloreactive antibody response.…”

Section: Discussionmentioning

confidence: 99%

T follicular helper expansion and humoral-mediated rejection are independent of the HVEM/BTLA pathway

et al. 2016

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Section: Discussionmentioning

confidence: 99%

T follicular helper expansion and humoral-mediated rejection are independent of the HVEM/BTLA pathway

et al. 2016

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“…A further experimental tolerogenesis model in mice demonstrated the expression of IL-10 in several organs including thymus, liver, and transplant, while FoxP3+ T cells were found inside the transplanted heart as late as 140 days after transplantation [145]. The IL-10 upregulation and Tregs generation in the tolerance of experimental cardiac allografts are also evidenced during treatment with danazol [144,148]. The production of suppressive cytokines like IL-10 did not avoid the liver allograft rejection, which has been associated with IFN-γ but not with expression of respective HLA markers [149].…”

Section: Principal Immune Conditionsmentioning

confidence: 91%

Regulator Versus Effector Paradigm: Interleukin-10 as Indicator of the Switching Response

Mingomataj

Bakiri

2015

Clinic Rev Allerg Immunol

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The interleukin-10 (IL-10) is generally considered as the most important cytokine with anti-inflammatory properties and one of the key cytokines preventing inflammation-mediated tissue damage. In this respect, IL-10 producing cells play a crucial role in the outcome of infections, allergy, autoimmune reactions, tumor development, and transplant tolerance. Based on recent findings with regard to the mentioned clinical conditions, this review attempts to shed some light on the IL-10 functions, considering this cytokine as inherent inducer of the switching immunity. While acute infections and vaccinations are associated by IL-10 enhanced during few weeks, chronic parasitoses, tumor diseases, allergen-specific immunotherapy, transplants, and use of immune-suppressor drugs show an increased IL-10 level along months or years. With regard to autoimmune pathologies, the IL-10 increase is prevalently observed during early stages, whereas the successive stages are characterized by reaching of immune equilibrium independently to disease's activity. Together, these findings indicate that IL-10 is mainly produced during transient immune conditions and the persistent IL-10-related effect is the indication/prediction (and maybe effectuation) of the switching immunity. Actual knowledge emphasizes that any manipulation of the IL-10 response for treatment purposes should be considered very cautiously due to its potential hazards to the immune system. Probably, the IL-10 as potential switcher of immunity response should be used in association with co-stimulatory immune effectors that are necessary to determine the appropriate deviation during treatment of respective pathologies. Hopefully, further findings would open new avenues to study the biology of this "master switch" cytokine and its therapeutic potential.

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“…Interestingly, a single administration of agonistic BTLA antibodies at the time of autologous haematopoietic stem cell transplantation prevents the development of graft- versus- host disease by the inhibition of CD4 + Foxp3 − effector T cell expansion [113]. Furthermore, agonistic BTLA antibodies prolong murine cardiac allograft survival by decreasing IL-2 and IFNγ production and shifting the differentiation towards the Treg phenotype [114]. Additionally to the function as receptor, BTLA can also behave as ligand.…”

Section: Inhibitory Receptors Associated With T Cell Exhaustionmentioning

confidence: 99%

T cell exhaustion: from pathophysiological basics to tumor immunotherapy

Klieser²,

et al. 2017

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The immune system is capable of distinguishing between danger- and non-danger signals, thus inducing either an appropriate immune response against pathogens and cancer or inducing self-tolerance to avoid autoimmunity and immunopathology. One of the mechanisms that have evolved to prevent destruction by the immune system, is to functionally silence effector T cells, termed T cell exhaustion, which is also exploited by viruses and cancers for immune escape In this review, we discuss some of the phenotypic markers associated with T cell exhaustion and we summarize current strategies to reinvigorate exhausted T cells by blocking these surface marker using monoclonal antibodies.

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An Agonistic Anti-BTLA mAb (3C10) Induced Generation of IL-10-Dependent Regulatory CD4+ T Cells and Prolongation of Murine Cardiac Allograft

Abstract: 3C10 could control acute rejection by its suppressive effect on alloreactive T cells and induction of IL-10-dependent regulatory CD4 T cells.

Cited by 35 publications

References 43 publications

T follicular helper expansion and humoral-mediated rejection are independent of the HVEM/BTLA pathway

T follicular helper expansion and humoral-mediated rejection are independent of the HVEM/BTLA pathway

Regulator Versus Effector Paradigm: Interleukin-10 as Indicator of the Switching Response

T cell exhaustion: from pathophysiological basics to tumor immunotherapy

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