Discovery of 101-s Pulsations from AX J0057.4-7325 in the SMC with ASCA

The results from two ASCA observations of AX J0057.4-7325 = RX J0057.3-7325 are presented. Coherent pulsations with a barycentric period of 101.45 +/- 0.07 s were discovered in the second observation. The X-ray spectrum was found to be hard (photon index ~ 0.9) and unchanged through these observations, except for the flux. The ROSAT archival data show that AX J0057.4-7325 exhibits a flux variation with a factor >~ 10. A discussion on a possible optical counterpart is given.Comment: 4 pages, 4 figures, to be published in PASJ. Also available at http://www-cr.scphys.kyoto-u.ac.jp/member/jun/job

スーパー抗原ブドウ球菌性腸管毒A応答性の4マウスT細胞画分のSEAによるアナジー誘導の感受性の解析

本研究でわれわれは細菌性スーパー抗原の黄色ブドウ球菌腸管毒素A (staphylococcal enterotoxin A, SEA)応答性のC57BL/6マウス脾臓Vβ3^+CD4^+, Vβ3^+CD8^+, Vβ11^+CD4^+,およびVβ11^+CD8^+T細胞のSEAによるアナジー誘導感受性を解析した.CD4^+T細胞はSEA刺激に対して,CD8^+T細胞と比べて,高レベルの増殖反応とIL-2産生反応を示した.CD4^+T細胞をSEAとインターロイキン-2で刺激して得られたCD4^+芽球化T細胞はSEA再刺激に対して高レベルの増殖反応とIL-2産生を示したが,同様な操作により得られたCD8^+芽球化T細胞はほとんど応答性を示さなかった.SEA誘導CD4^+芽球化T細胞から得られたVβ3^+CD4^+芽球化T細胞はSEA刺激に対して高レベルの増殖反応とIL-2産生を示したが,同様にして得られたVβ11^+CD4^+芽球化T細胞は無反応であった.本研究によって,Vβ3^+CD4^+T細胞はSEAによるアナジー誘導に抵抗性であり,他の3種のSEA応答性T細胞画分は高感受性であることが判明した.SEA応答性マウスT細胞画分のSEAによるアナジー誘導の感受性はレセプターVβ表現とCD4/CD8サブセットによって大きく影響を受けると考えられた.In the present study, we analyzed susceptibility to the in vitro induction of anergy by a superantigen (SAG), staphylococcal enterotoxin A (SEA), in SEA-reactive murine Vβ3^+CD4^+, Vβ3^+CD8^+, Vβ11^+CD4^+, and Vβ11^+CD8^+ T cells. CD4^+ T cells exhibited a high proliferative response and IL-2 production upon primary stimulation with SEA, while CD8^+ T cells exhibited only low responses. CDC T cell blasts prepared by stimulating CD4^+ T cells with a combination of SEA and IL-2 were highly responsive to restimulation with SEA, while CD8^+ T cell blasts prepared in the same way were unresponsive. Vβ3^+CD4^+ T cell blasts prepared from SEA-induced CD4^+ T cell blasts were highly responsive to restimulation with SEA, while Vβ11^+CD4^+ T cell blasts prepared in the same manner were unresponsive. These results indicate that Vβ3^+CD4^+ T cells have a low susceptibility while other three SEA-reactive T cell fractions have a high susceptibility to anergy induction with SEA. The susceptibility to anergy induction by a certain SAG in several distinct T cell fractions reactive with that SAG is probably influenced largely by the expression of Vβ elements and the CD4/CD8 subsets

Specific Inhibitory Action of Anisodamine against a Staphylococcal Superantigenic Toxin, Toxic Shock Syndrome Toxin 1 (TSST-1), Leading to Down-Regulation of Cytokine Production and Blocking of TSST-1 Toxicity in Mice

Toxic shock syndrome toxin 1 (TSST-1), produced by Staphylococcus aureus (including methicillin-resistant S. aureus), is a superantigenic toxin responsible for toxic shock syndrome as well as neonatal TSS-like exanthematous disease. TSST-1 exhibits its deleterious effects by leading to the abnormal proliferation of, e.g., Vβ2(+) T cells and overproduction of proinflammatory cytokines. In the present study we examined the inhibitory effect of a Chinese herbal extract, anisodamine, on TSST-1 using human peripheral blood mononuclear cells (PBMCs). Anisodamine inhibited the production of proinflammatory cytokines better than interleukin-10 (an anti-inflammatory cytokine). The inhibitory effect of anisodamine was greater than that of any tropane alkaloid examined. Anisodamine acted directly on both monocytes and T cells in human PBMCs, and the effect was confirmed at the transcriptional level. Inhibition of NF-κB activation was also demonstrated. In contrast, no significant inhibition of Vβ2(+) T-cell proliferation was observed. In mice injected with TSST-1, anisodamine treatment significantly decreased serum proinflammatory cytokine levels and prevented TSST-1-induced death. These results suggest that anisodamine specifically acts against the production of cytokines (inflammatory cytokines in particular) and not against Vβ2(+) T-cell proliferation and that anisodamine may have a beneficial effect on TSST-1-associated disease

細菌性スーパー抗原黄色ブドウ球菌腸管毒素A(SEA)に応答するいくつかのマウスT細胞集団はSEA刺激に対する応答性が異なる

我々はスーパー抗原,黄色ブドウ球菌腸管毒素A(SEA)2回投与の影響をC57BL/6,β^+ミクログロブリンノックアウトおよびCD4ノックアウトマウスを用いて検討した.1回目のSEA投与では,SEA応答性T細胞4画分(Vβ3^+D4^+,Vβ3^+D8^+,Vβ11^+CD4^+,Vβ11^+CD8^+)は共に投与2日目をピークに増幅し,その後対照のレベルまで減少する.しかし,1回目の投与後,2日目にSEAを再投与するとSEA応答性T細胞画分はそれぞれ異なった反応を示した.増幅したVβ3^+CD4^+細胞はさらに投与後2日目まで増幅した.増幅したVβ3^+CD8^+およびVβ11^+CD4^+T細胞は再投与後2日目まで増幅した状態を維持した.一方,増幅したVβ11^+CD8^+T細胞は再投与後,すぐに減少した.SEA2回目投与後,3時間目の各細胞集団のIL-2レセプターα鎖の発現量はVβ3^+CD4^+およびVβ11^+CD4^+T細胞で90%以上,Vβ3^+CD8^+T細胞では約80%,Vβ11^+CD8^+T細胞では約70%であり,これらの細胞集団の大多数はSEA認識能力を保持していた.以上の結果より,Vβ11^+CD8^+T細胞のアナジー感受注は著しく高く,Vβ3^+CD4^+T細胞は低く,Vβ3^+CD8^+およびVβ11^+CD4^+T細胞はその中間であろうと推測した.We examined the immunologic behaviors of a superantigen Staphylococcal enterotoxin A (SEA)-reactive four distinct T cell populations (Vβ3^+CD4^+, Vβ3^+CD8^+, Vβ11^+CD4^+ and Vβ11^+CD8^+ T cells) in mice injected with SEA twice in a 2-day interval. The four T cell populations increased equally at 2 days after the first injection and thereafter decreased equally to the control level. However, these four T cell populations expanded by the first SEA injection exhibited different behaviors upon the second SEA injection, depending on the T cell receptor Vβ elements expressed and the T cell subsets. Vβ3^+CD4^+ T cells expanded exhibited further expansion, and Vβ11^+CD8^+ T cells expanded decreased rapidly. Vβ3^+CD8^+ and Vβ11^+CD4^+ T cells expanded were sustained in similar levels for 2 days after the second injection. Peak of serum IL-2 activity was seen in a higher level and at earlier hours after the second SEA injection than the first injection. Levels of IL-2 receptor a chain expression were more than 90% in Vβ3^+CD4^+ T cells and Vβ11^+CD4^+ T cells, about 80% in Vβ3^+CD8^+ T cells, and about 70% in Vβ11^+CD8^+ T cells, suggesting that large parts of these T cell populations can recognized SEA. These results suggest that Vβ3^+CD4^+ T cells are low and Vβ11^+CD8^+ T cells are high in the susceptibility to anergic induction with SEA. Vβ3^+CD8^+ and Vβ11^+CD4^+ T cells may be sustained at intermediate level

ヒトCD4+T細胞のスーパー抗原によるTh1,Th2 type細胞への偏向

免疫応答に重要な役割をもつCD4+ヘルパーT細胞に2つのサブセット(Th1,Th2)があり, Th1/Th2バランスの変調が,様々な疾患の病因に大きく関与していることが明らかになってきた.これまで,人工的な刺激物質である抗CD3抗体などを用いてin vitro実験系で偏向させたヒトTh1細胞とTh2細胞サンプルを得るまでに4週間ほど時間が必要であった.本研究では自然環境においてヒトT細胞の強力な活性化抗原である細菌性スーパー抗原を用い,短期間にTh1細胞とTh2細胞を誘導できる実験システムを確立した.ヒトT細胞の未感作分画であるCD4^+CD45RA^+T細胞は1週間以内にTh1細胞とTh2細胞に分化を遂げた.一方,末梢血感作T細胞分画であるCD4^+CD45RO^+T細胞はTh1/Th2偏向刺激に対して抵抗性を示した.ケモカインレセプター表現の解析では,従来の報告と同様にCD4^+CD45RA^+T細胞から誘導されたTh1細胞はCXCR3陽性であり,Th2細胞はCXCR3陰性を示す成績が得られた.また,Th1/Th2偏向刺激を受けたCD4^+CD45RO^+T細胞は,いずれにおいてもCXCR3陽性細胞とCXCR3陰性細胞が混在していた.To induce T-helper type 1 (Th1) and type 2 (Th2) cells in a short period, human adult peripheral blood T cells were cultured in combination with toxic shock syndrome toxin-1 (TSST-1) in the presence of IL-12 and anti-IL-4 antibody (Th1-polarizing condition), or in combination with IL-4, anti-IL-12 and anti-IFN-γ antibodies (Th2-polarizing condition) in the presence of IL-2 for a total of 7 days. CD4^+ T cell blasts that resulted from the Th1-polarizing condition of unprimed type CD4^+CD45RA^+ T cells exhibited massive IFN-γ production but quite low IL-4 production upon re-stimulation with TSST-1. Around 90% of the cells that exhibited the typical Th1 response were CXCR3-positive. These cells were divided into CCR4-positive and CCR4-negative fractions. The CD4^+ T cell blasts that resulted from the Th2-polarizing condition exhibited massive IL-4 production but quite low IFN-γ production. Around 70% of the cells that exhibited the typical Th2 response were CXCR3-negative but were CCR4-positive. Two preparations of CD4^+ T cell blasts resulting from the Th1 and the Th2 polarizing conditions of the memory-type CD4^+CD45RO^+ T cells produced both IFN-γ and IL-4 in substantial units and contained both CXCR3-positive and CXCR3-negative cells. The results indicated that the new system induced typical Th1 and Th2 cells from unprimed CD4^+ T cells within 7 days and that the expression of CXCR3 was the key factor to discriminate Th1 and Th2 cells