ヒト細胞傷害性T細胞の異なる発達段階での免疫機能

CD8陽性の細胞傷害性T細胞(CTL)は,ウイルス感染細胞や腫瘍細胞の排除などの免疫応答において重要な役割を演じる,しかしその機能的な成熟に関しては,不明である.我々は,以前in vitro培養系において,細菌性スーパー抗原,毒素性ショック症候群毒素-1(TSST-1)の一次刺激で得られた成人末梢血由来CD4陽性T細胞芽球が,TSST-1の再刺激に対し強い増殖とサイトカイン産生を示すのに対し,臍帯血および胸腺由来のCD4陽性T細胞芽球は,両反応において無反応性(アナジー)を示し機能的に未熟であることを見出した.本研究は,同様の実験系を用いてヒトCD8陽性T細胞の機能的成熟について明らかにすることを目的とした.TSST-1刺激で得られた成人末梢血CD8陽性T細胞芽球は,TSST-1再刺激に対する増殖およびサイトカイン(TNF-α,IFN-γ)産生,TSST-1特異的なヒトB細胞(Daudi細胞)傷害において強い反応を示した.一方,臍帯血および胸腺CD8陽性T細胞芽球は,増殖でアナジーを認め,臍帯血CD8陽性T細胞芽球は,低サイトカイン産生を示した.細胞傷害活性は両者とも,成人末梢血CD8陽性T細胞芽球と同レベルの誘導を認めた.また,早産の臍帯血CD8陽性T細胞芽球も成人末梢血CD8陽性T細胞芽球と同レベルの細胞傷害活性を認めた.以上の結果から,ヒト臍帯血および胸腺CD8陽性T細胞は,CD4陽性T細胞と同様な機能的未熟性を有することが明らかになった.しかし,異物の排除に係る細胞傷害活性は,成人末梢血CD8陽性T細胞と同レベルに誘導されることを見出した.一般に末梢リンパ組織においてT細胞が機能的に成熟するためには出生後ある程度の時間を要することが示唆されている.したがって,本研究の結果は,新生児CD8陽性T細胞の免疫応答を理解するための有用な情報になると考えられる.Cytotoxic T lymphocytes (CTLs) play an important role in immune responses, and provide potent defenses against virus infection and intracellular pathogens. However, as compared with helper T lymphocytes, CTL development remains to be clarified. In this study we tried to find out the differences in maturity of human thymus, cord blood (CB), and adult peripheral blood (APB)-derived CD8^+ T cells, and examined whether these T cells are vulnerable or not to anergy induction. Using toxic shock syndrome toxin-1 (TSST-1), CD8^+ T cell blasts with different origins were prepared and re-stimulated to estimate their immunological responses. The results showed that the proliferative response and TNF-α production upon re-stimulation with TSST-1 in thymic and CB CD8^+ T cell blasts were much lower than those of APB, although the capacity for cytotoxic activity was comparable at all three different stages of T cell development. Therefore, thymic and CB CD8^+ T cells obviously had immature traits, but appeared to have the capacity to eliminate pathogenic factors in terms of cytotoxic activity

ヒト細胞傷害性T細胞の異なる発達段階での免疫機能

CD8陽性の細胞傷害性T細胞(CTL)は,ウイルス感染細胞や腫瘍細胞の排除などの免疫応答において重要な役割を演じる,しかしその機能的な成熟に関しては,不明である.我々は,以前in vitro培養系において,細菌性スーパー抗原,毒素性ショック症候群毒素-1(TSST-1)の一次刺激で得られた成人末梢血由来CD4陽性T細胞芽球が,TSST-1の再刺激に対し強い増殖とサイトカイン産生を示すのに対し,臍帯血および胸腺由来のCD4陽性T細胞芽球は,両反応において無反応性(アナジー)を示し機能的に未熟であることを見出した.本研究は,同様の実験系を用いてヒトCD8陽性T細胞の機能的成熟について明らかにすることを目的とした.TSST-1刺激で得られた成人末梢血CD8陽性T細胞芽球は,TSST-1再刺激に対する増殖およびサイトカイン(TNF-α,IFN-γ)産生,TSST-1特異的なヒトB細胞(Daudi細胞)傷害において強い反応を示した.一方,臍帯血および胸腺CD8陽性T細胞芽球は,増殖でアナジーを認め,臍帯血CD8陽性T細胞芽球は,低サイトカイン産生を示した.細胞傷害活性は両者とも,成人末梢血CD8陽性T細胞芽球と同レベルの誘導を認めた.また,早産の臍帯血CD8陽性T細胞芽球も成人末梢血CD8陽性T細胞芽球と同レベルの細胞傷害活性を認めた.以上の結果から,ヒト臍帯血および胸腺CD8陽性T細胞は,CD4陽性T細胞と同様な機能的未熟性を有することが明らかになった.しかし,異物の排除に係る細胞傷害活性は,成人末梢血CD8陽性T細胞と同レベルに誘導されることを見出した.一般に末梢リンパ組織においてT細胞が機能的に成熟するためには出生後ある程度の時間を要することが示唆されている.したがって,本研究の結果は,新生児CD8陽性T細胞の免疫応答を理解するための有用な情報になると考えられる.Cytotoxic T lymphocytes (CTLs) play an important role in immune responses, and provide potent defenses against virus infection and intracellular pathogens. However, as compared with helper T lymphocytes, CTL development remains to be clarified. In this study we tried to find out the differences in maturity of human thymus, cord blood (CB), and adult peripheral blood (APB)-derived CD8^+ T cells, and examined whether these T cells are vulnerable or not to anergy induction. Using toxic shock syndrome toxin-1 (TSST-1), CD8^+ T cell blasts with different origins were prepared and re-stimulated to estimate their immunological responses. The results showed that the proliferative response and TNF-α production upon re-stimulation with TSST-1 in thymic and CB CD8^+ T cell blasts were much lower than those of APB, although the capacity for cytotoxic activity was comparable at all three different stages of T cell development. Therefore, thymic and CB CD8^+ T cells obviously had immature traits, but appeared to have the capacity to eliminate pathogenic factors in terms of cytotoxic activity

Outer Membrane Protein of Gut Commensal Microorganism Induces Autoantibody Production and Extra-Intestinal Gland Inflammation in Mice

Gut commensal microorganisms have been linked with chronic inflammation at the extra-intestinal niche of the body. The object of the study was to investigate on the chronic effects of a gut commensal Escherichia coli on extra-intestinal glands. The presence of autoimmune response was diagnosed by autoantibody levels and histological methods. Repeated injection of E. coli induced mononuclear cell inflammation in the Harderian and submandibular salivary glands of female C57BL/6 mice. Inflammation was reproduced by adoptive transfer of splenocytes to immune-deficient Rag2 knockout mice and CD4+ T cells to mature T cell-deficient TCRβ-TCRδ knockout mice. MALDI TOF mass spectrometry of the protein to which sera of E. coli-treated mice reacted was determined as the outer membrane protein A (OmpA) of E. coli. Multiple genera of the Enterobacteriaceae possessed OmpA with high amino-acid sequence similarities. Repeated injection of recombinant OmpA reproduced mononuclear cell inflammation of the Harderian and salivary glands in mice and elevation of autoantibodies against Sjögren’s-syndrome-related antigens SSA/Ro and SSB/La. The results indicated the possibility of chronic stimuli from commensal bacteria-originated components as a pathogenic factor to elicit extra-intestinal autoimmunity

Detection limit of computed tomography for hepatoblastoma pulmonary metastases: Based on total resection using indocyanine green fluorescence

Background: Intraoperative search for small pulmonary metastases of hepatoblastoma has been challenging; therefore, it has been difficult to determine the true detection limit of computed tomography (CT). This is the first report on the detection limit of CT for hepatoblastoma pulmonary metastases in patients who underwent resection of hepatoblastoma pulmonary metastases using indocyanine green fluorescence (ICGF). Methods: We retrospectively reviewed the CT images of patients who underwent resection of hepatoblastoma pulmonary metastases using ICGF between January 2013 and November 2021 at a single children's hospital and compared them with pathological findings. Results: Overall, 757 nodules were resected from 20 cases and 75 thoracotomies; 411 nodules were considered for the study and 286 were pathologically positive. The number of nodules classified by size in the pathological sections and the probability of CT detection were as follows: 3 mm were detectable on CT, whereas less than 30 % of pathologically positive nodules < 2 mm could be detected. In children with hepatoblastoma, a CT-positive pulmonary nodule, even if minute, is likely to be malignant and metastasis should be suspected

Case report: Hepatectomy with Rex bypass for a child with hepatoblastoma and portal vein thrombosis

Pediatric liver tumors with portal vein obstruction are often candidates for liver transplantation. However, lifelong use of immunosuppressants and invasiveness to healthy donors in the case of living-donor liver transplantation is inevitable. Moreover, when lung metastasis is involved, the lung recurrence rate after liver transplantation is still high. Therefore, transplantation should be avoided as much as possible. In cases of tumors in the right lobe of the liver, complete resection of the portal vein trunk may be possible by creating a Rex bypass, but with the original method, end-to-side anastomosis to the umbilical portal vein is difficult in small children. We report a case of a 2-year-old girl with hepatoblastoma in whom a Rex shunt was created by end-to-end anastomosing the recanalized umbilical vein to the portal vein stump with interposing a vein graft, and the right lobe was successfully resected along with the tumor