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Pathogenesis of childhood idiopathic nephrotic syndrome:a paradigm shift from T-cells to podocytes

World Journal of Pediatrics 2015年第1期11卷 21-28页

作者： Kazunari kaneko Shoji Tsuji Takahisa Kimata Tetsuya Kitao Sohsaku Yamanouchi Shogo Kato Department of Pediatrics Kansai Medical University2-5-1 Shin-machiHirakataOsaka 573-1010Japan

Background:Nephrotic syndrome is the most common cause of kidney disease in children,but its pathogenesis remains *** article reviews the novel aspects of the mechanisms underlying massive proteinuria in minimal-change disease,which is the most common form of childhood nephrotic *** sources:This article integrates the findings of a PubMed database search for English language articles published in the past 40 years(from September 1974 to February 2014)using the key words"pathogenesis","minimal change nephrotic syndrome"or"idiopathic ne phrotic syndrome".Results:Unknown humoral factors associated with T-cell dysfunction have been thought to play an important role in the pathogenesis of minimal-change ***,recent findings are changing this paradigm,i.e,visceral glomerular epithelial cells(podocytes)may be involved via expression of molecules such as CD80 and angiopoietin-like ***:Recent evidence suggests that minimal-change disease results from interactions between humoral factors and dysfunctional *** addition to immunosuppressant drugs that target lymphocytes,a biological agent such as an antibody against the abnormal molecule(S)expressed by podocytes may provide novel drug treatment for minimal-change disease.

关键词： angiopoietin-like 4 CD80 cytokine minimal change nephrotic syndrome podocyte

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BCR–ABL-specific CD4^(+) T-helper cells promote the priming of antigen-specific cytotoxic T cells via dendritic cells

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Cellular & Molecular Immunology 2018年第1期15卷 15-26页

作者： Norihiro Ueda Rong Zhang Minako Tatsumi Tian-YiLiu Shuichi Kitayama YutakaYasui Shiori Sugai Tatsuaki Iwama Satoru Senju Seiji Okada Tetsuya Nakatsura Kiyotaka Kuzushima Hitoshi Kiyoi Tomoki Naoe shin kaneko Yasushi Uemura Division of Immunology Aichi Cancer Center Research InstituteNagoya464-0021Japan shin kaneko laboratory Department of Cell Growth and DifferentiationCenter for iPS cell Research and Application(CiRA)Kyoto UniversityKyoto606-8507Japan Department of Hematology and Oncology Nagoya University Graduate School of MedicineNagoya466-0065Japan Division of Cancer Immunotherapy Exploratory Oncology Research&Clinical Trial CenterNational Cancer CenterKashiwa277-8577ChibaJapan Key laboratory of Cancer Center Chinese PLA General HospitalBeijing100853China Department of Immunogenetics Graduate School of Medical SciencesKumamoto UniversityKumamoto860-8556Japan Division of Hematopoiesis Center for AIDS ResearchKumamoto UniversityKumamoto860-0811Japan National Hospital Organization Nagoya Medical Center Nagoya460-0001Japan

The advent of tyrosine kinase inhibitor(TKI)therapy markedly improved the outcome of patients with chronic-phase chronic myeloid leukemia(CML).However,the poor prognosis of patients with advanced-phase CML and the lifelong dependency on TKIs are remaining challenges;therefore,an effective therapeutic has been *** BCR–ABL p210 fusion protein’s junction region represents a leukemia-specific neoantigen and is thus an attractive target for antigen-specific T-cell ***–ABL p210 fusion-region-specific CD4+T-helper(Th)cells possess antileukemic potential,but their function remains *** this study,we established a BCR–ABL p210 b3a2 fusion-region-specific CD4+Th-cell clone(b3a2-specific Th clone)and examined its dendritic cell(DC)-mediated antileukemic *** b3a2-specific Th clone recognized the b3a2 peptide in the context of HLA-DRB1*09:01 and exhibited a Th1 *** of this clone through T-cell antigen receptor stimulation triggered DC maturation,as indicated by upregulated production of CD86 and IL-12p70 by DCs,which depended on CD40 ligation by CD40L expressed on b3a2-specific Th ***,in the presence of HLA-A*24:02-restricted Wilms tumor 1(WT1)235–243 peptide,DCs conditioned by b3a2-specific Th cells efficiently stimulated the primary expansion of WTI-specific cytotoxic T lymphocytes(CTLs).The expanded CTLs were cytotoxic toward WT1235–243-peptide-loaded HLA-A*24:02-positive cell lines and exerted a potent antileukemic effect in ***,the b3a2-specific Th-clone-mediated antileukemic CTL responses were strongly inhibited by both TKIs and interferon-α.Our findings indicate a crucial role of b3a2-specific Th cells in leukemia antigen-specific CTL-mediated immunity and provide an experimental basis for establishing novel CML immunotherapies.

关键词： BCR-ABL cancer immunotherapy CML dendritic cell T helper cell

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Is the CD4/CD8 Ratio an Effective Indicator for Clinical Estimation of Adoptive Immunotherapy for Cancer Treatment?

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Journal of Cancer Therapy 2013年第8期4卷 1382-1390页

作者： Goki shindo Takayoshi Endo Masamitsu Onda Shigenori Goto Yoju Miyamoto Toru kaneko Cardiothoracic Department Meditopia Numazu Clinic Numazu Japan Department of Immunotherapy Seta Clinic Shin-Yokohama Yokohama Japan Department of Immunotherapy Seta Clinic Tokyo Tokyo Japan

Background: The importance of immunotherapy in cancer treatment has been increased owing to its non-toxicity and application to personalized medicine. However, precise estimation indices of immunotherapy have yet to be established. To determine effective evaluation indices of immunotherapy for cancer treatment, we analyzed the CD4/CD8 ratio under various conditions in clinical patients with advanced cancer. Patients and Methods: Thirty-four patients who underwent one course of adoptive activated immunotherapy with or without additional conventional chemotherapy were enrolled. Before and after one course of immunotherapy, changes in the CD4/CD8 ratio were estimated by flow cytometry. Results: All patients showed a tendency toward a decrease in the CD4/CD8 ratio during a 3-month period after one course of adoptive activated T lymphocyte immunotherapy. Patients who had undergone prior surgery showed a remarkable increase in CD8 T cell number. Thus, adoptive activated T lymphocyte immunotherapy improves immunological ability against cancer invasion. The Eastern Cooperative Oncology Group’s performance status during one course of immunotherapy was significantly improved in the antecedent surgery group, with no evidence of improved PS in the non-antecedent surgery group. Patients with an increased CD4/CD8 ratio (n = 6) may have a worse outcome during adoptive activated T lymphocyte immunotherapy even with an additional course of immunotherapy. Improved actuarial survival rate of patients in the antecedent surgery group showed significant long-term benefit compared to those in the non-antecedent surgery group (p = 0.0298), as previously reported. Conclusion: The CD4/CD8 ratio is a significant indicator of outcome of adoptive activated T lymphocyte immunotherapy.

关键词： Immunotherapy Adoptive Activated T Lymphocyte therapy Flow Cytometry Performance Status Advanced Cancer

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