Isatis tinctoria L. combined with co-stimulatory molecules blockade prolongs survival of cardiac allografts in alloantigen-primed mice

Kang, Xiangpeng; Chen, Jibing; Qin, Qing; Wang, Feng; Wang, Yongzhi; Lan, Tianshu; Wang, Feiyu; Xia, Junjie; Ekberg, Henrik; Qi, Zhongquan; Liu, Zhongchen

doi:10.1016/j.trim.2010.03.006

Cited by 9 publications

(6 citation statements)

References 29 publications

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“…We then evaluated the effect of combining CD44/CD70 blockade and anti‐CD154/LFA‐1 treatment on the accelerated rejection in adoptive transfer recipients. Consistent with recent reports [22, 23] that memory T cells resist anti‐CD154L/LFA‐1 treatment, our analysis of allograft survival showed that the MST of grafts was only 21.5 days in adoptive transfer recipients treated with anti‐CD154/LFA‐1. While CD44/CD70 blockade prevented rejection mediated by CD4 + and CD8 + memory T cells, respectively [12, 15], anti‐CD154/LFA treatment combined with CD44 or CD70 blockade did not further prolong allograft survival over that achieved with anti‐CD154/LFA‐1 treatment alone in the presence of both CD4 + and CD8 + memory T cells.…”

Section: Discussionsupporting

confidence: 92%

CD44/CD70 Blockade and Anti‐CD154/LFA‐1 Treatment Synergistically Suppress Accelerated Rejection and Prolong Cardiac Allograft Survival in Mice

et al. 2011

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Current treatments that are efficient in controlling effector T cell responses to allografts have limited efficacy on the accelerated rejection mediated by memory T cells. Effective targeting of alloreactive memory T cells may therefore be explored to improve therapeutic approaches towards solving this problem. In this study, we investigated the synergistic effect of CD44/CD70 blockade and anti‐CD154/LFA‐1 treatment on the accelerated rejection mediated by memory T cells. While CD44/CD70 blockade had limited effects on the alloresponses of effector T cells in vivo, it diminished the expansion of both CD4+ and CD8+ memory T cells in recipients adoptively transferred with donor‐sensitized T cells. In combination with anti‐CD154/LFA‐1 treatment, CD44/CD70 blockade significantly prolonged cardiac allograft survival in adoptive transfer recipients. We demonstrated that treatment with the combination of all four antibodies (anti‐CD154/LFA‐1/CD44/CD70) inhibited accelerated rejection by markedly suppressing the alloresponses of effector and memory T cells and reducing the number of graft‐infiltration lymphocytes in adoptive transfer recipients. Meanwhile, CD44/CD70 blockade and anti‐CD154/LFA‐1 treatment synergically enhanced regulatory T cells (Tregs) by increasing the proportion of splenic Tregs and the expression of IL‐10 in these recipients. Our findings contribute to the potential design of therapies for accelerated allograft rejection.

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Section: Discussionsupporting

confidence: 92%

CD44/CD70 Blockade and Anti‐CD154/LFA‐1 Treatment Synergistically Suppress Accelerated Rejection and Prolong Cardiac Allograft Survival in Mice

et al. 2011

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“…However, Raptiva ® has been associated with an increased risk of progressive leukoencephalopathy(PML) which is a fatal disease of the central nervous system, therefore; it was withdrawn from the market in mid-2009 (12). Both monotherapy of anti-LFA-1 and combination therapy with anti-ICAM-1 antibody were effective in promoting long-term survival of islet, cardiac, small bowel and nerve allografts in animal models (1, 13–17). Treatment with anti-LFA-1 antibodies has shown disease prevention in animal models with autoimmune encephalomyelitis and autoimmune diabetes and has shown benefits in lupus and inflammatory arthritis (1, 18–22).…”

Section: Function Of Lfa-1 and Its Role In Diseasesmentioning

confidence: 99%

LFA-1 on Leukemic Cells as a Target for Therapy or Drug Delivery

Phongpradist¹,

Chittasupho²,

Okonogi³

et al. 2010

CPD

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Leukemia therapeutics are aiming for improved efficacy by targeting molecular markers differentially expressed on cancerous cells. Lymphocyte function-associated antigen-1 (LFA-1) expression on various types of leukemia has been well studied. Here, the role and expression of LFA-1 on leukemic cells and the possibility of using this integrin as a target for drug delivery is reviewed. To support this rationale, experimental results were also included where cIBR, a cyclic peptide derived from a binding site of LFA-1, was conjugated to the surface of polymeric nanoparticles and used as a targeting ligand. These studies revealed a correlation of LFA-1 expression level on leukemic cell lines and binding and internalization of cIBR-NPs suggesting a differential binding and internalization of cIBR-NPs to leukemic cells overexpressing LFA-1. Nanoparticles conjugated with a cyclic peptide against an accessible molecular marker of disease hold promise as a selective drug delivery system for leukemia treatment.

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“…It augments maturation of DCs to competent APCs, a prerequisite for the generation of adaptive immunity and also a major function of adjuvant. Further evidence has shown that poly I:C potently activates and boosts memory CD8 [10] and CD4 T cells [11,12] through the activation of DCs that produce an array of cytokines, including IL-12 and type 1 IFNs [7,13]. Therefore, in recent years, poly I:C has been preferentially used as one of the most potent adjuvants for vaccines [11,14,15].…”

Section: Introductionmentioning

confidence: 99%

Length of dsRNA (poly I:C) drives distinct innate immune responses, depending on the cell type

Mian

Ahmed

Rad

et al. 2013

Journal of Leukocyte Biology

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Poly I:C, a synthetic dsRNA analogue, has been used extensively for decades to study innate responses in vivo and in different cell types. We have found substantial variability while using poly I:C from different sources. In this study we found that poly I:C from 2 commercial sources induced sharply opposite responses in myeloid and fibroblasts, depending on the length of the poly I:C. Although short poly I:C (≈ 1-1.5 kb) induced greater amounts of TNF-α, IL-8, and IFN-β and a stronger antiviral response in myeloid cells, it was a poor inducer in fibroblasts. By contrast, long poly I:C (>5 kb) preferentially elicited higher cytokine and antiviral responses in fibroblasts and showed diminished responses in myeloid cells. Poly I:C activated NF-κB and STAT-1 signaling in a length- and cell-type-dependent fashion. Mechanistically, short poly I:C was better internalized in the myeloid cells and long poly I:C in the fibroblasts. Finally, long poly I:C required SR-A, whereas short poly I:C required RIG-I and Raftlin. We provide evidence that the length of dsRNA drives distinct innate responses in different cell lineages. These findings may augment in selecting the appropriate poly I:C type to design cell-type-specific potent adjuvants for vaccines against infectious diseases or cancers.

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Isatis tinctoria L. combined with co-stimulatory molecules blockade prolongs survival of cardiac allografts in alloantigen-primed mice

Cited by 9 publications

References 29 publications

CD44/CD70 Blockade and Anti‐CD154/LFA‐1 Treatment Synergistically Suppress Accelerated Rejection and Prolong Cardiac Allograft Survival in Mice

CD44/CD70 Blockade and Anti‐CD154/LFA‐1 Treatment Synergistically Suppress Accelerated Rejection and Prolong Cardiac Allograft Survival in Mice

LFA-1 on Leukemic Cells as a Target for Therapy or Drug Delivery

Length of dsRNA (poly I:C) drives distinct innate immune responses, depending on the cell type

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