^147Pm诱发体细胞和生殖细胞的UDS效应

本文研究了机体摄入不同放射性活度的荧光涂料激发能源１４７Ｐｍ时，诱发外周免疫器官脾淋巴细胞和生殖细胞精子的ＵＤＳ效应。观察结果表明，当机体摄入１４７Ｐｍ的放射性活度处在３．７×１０１～１．８５×１０２Ｂｑ／ｇ体重时，可使ＵＶ诱发脾淋巴细胞和精子的ＵＤＳ值明显增升，使ＤＮＡ的修复能力增强。可是，随着１４７Ｐｍ摄入放射性活度进一步增大至３．７×１０３Ｂｑ／ｇ体重时，观察到ＵＶ诱发的脾淋巴细胞和精子细胞的ＵＤＳ值都呈明显下降，呈现抑制效应，表明１４７Ｐｍ使脾淋巴细胞和精子的ＤＮＡ修复能力受到损伤。     

Intestinal T lymphocytes in the chicken express an integrin-like antigen

We report the characterization of a molecule recognized on chicken T cells by the murine A19 monoclonal antibody that was generated by immunization with intestinal intraepithelial lymphocytes. Immunofluorescence analysis indicated that both αβ and γδ T cell subpopulations in the intestine express the A19 antigen, but natural killer cells and B cells do not. The A19-marked T cells were preferentially localized in the intestinal epithelium and less frequently in the underlying lamina proprial, T cells appearing in the intestine during embryonic life were A19 negative but acquired the antigen within the first few days after hatching. Although rarely found on cells in non-intestinal tissues at any age, very late expression of the A19 antigen could be induced by concanavalin A stimulation of splenic and circulating T cells. Transforming growth factor β1 enhanced this induction of A19 expression. The A19 molecules expressed by intestinal T cells and activated splenic T cells were biochemically identical, consisting of a multi-molecular complex of proteins with approximate M_r of 205, 145 and 75 kDa under nonreducing conditions and 120, 90 and 28 kDa under reducing conditions. The characteristics of this multimolecular complex and its differential expression suggest that the A19 antigen is a member of the integrin family which may function in the retention of intestinal lymphocytes.     

High grade malignant lymphoma with clinical characteristics and immunophenotype of natural killer cells

The malignant proliferation of natural killer (NK) cells which are morphologically characterized as large granular lymphocytes (LGL) is a well known clinical entity which was named after its morphological appearance as LGL-leukemia/lymphoma. Similar to non-malignant NK-cells, these tumors can be divided into those which express the CD3-T-cell receptor complex and those which do not. The CD3-positive type of LGL-leukemia is immunophenotypologically characterized by the expression of CD16, and variably CD 56 and CD 57, and generally follows a more indolent course. In contrast, malignant proliferations of CD3-negative LGL express either CD16 or CD 56, and only occasionally CD 57 on their cell surface. Clinically, CD3-negative NK-lymphomas tend to progress rapidly. We report here the case of a high grade malignant lymphoma which was characterized by an immunophenotype typical for CD3-negative NK-cells (CD2+, CD3?, CD16+, CD56(+), CD57?). The disease proved to be rapidly fatal despite aggressive chemotherapy. Interestingly, the patient suffered from a high turn over pancytopenia, which also characterizes NK-cell leukemias/lymphomas of the LGL-type. However, our patient's lymphatic cells appeared highly immature, and cytoplasmic granules, characteristic for LGL-cells, could not be discerned either microscopically or electronmicroscopically. Furthermore, the malignant lymphatic population had the T-cell receptor α-chain rearranged. We therefore concluded that our patient might have suffered from a malignant proliferation of a putative precursor cell intermediate between T-cells and NK-cells. © 1995 Wiley-Liss, Inc.     

原发性肝癌肿瘤浸润淋巴细胞的分离培养及抗瘤活性研究

为了解原发性肝癌肿瘤浸润淋巴细胞治疗肝癌的临床价值及应用前景，采用Ｒｏｓｅｎｂｅｒｇ法，对ＴＩＬ细胞的分离，培养及抗瘤活性进行了研究。结果８例肝癌病人的ＴＩＬ细胞分离，培养均获得成功，并在培养３－５周后扩增到临床治疗肝癌后需的ＴＩＬ细胞数量。     

呋塞米吸入治疗对老年慢性哮喘患者肺功能和外周血T淋巴细胞亚群的影响

目的评价呋塞米（速尿）吸入对老年人慢性哮喘的治疗效果。方法７２例老年慢性哮喘患者分别给予速尿（Ａ组）、速尿＋溴化异丙托品（Ｂ组）和溴化异丙托品（Ｃ组）治疗，每组各２４例，并与６０例非老年慢性哮喘患者的结果进行比较。吸入前后测肺功能〔最大肺活量（ＦＶＣ）、一秒钟最大呼气量（ＦＥＶ１）、最大呼气流速（ＰＥＦＲ）〕和外周血Ｔ细胞亚群。结果老年组总有效率（有效＋显效），Ａ、Ｂ、Ｃ组分别为７５％、９２％、６７％。肺功能和Ｔ细胞亚群改变：Ａ组ＦＥＶ１和ＣＤ４吸入前后变化差异有显著性（Ｐ＜００５）；Ｂ组肺功能指标和ＣＤ４、ＣＤ８、ＣＤ４／ＣＤ８差异有非常显著性（Ｐ＜００１或０００１）；Ｃ组除ＰＥＦＲ有显著变化（Ｐ＜００５）外，余项也有改善，但无统计学意义。非老年组的疗效与老年组疗效基本相同。结论速尿吸入对老年人慢性哮喘有防治作用，特别是速尿＋溴化异丙托品联合吸入效果更好     

Phenotypic and functional characteristics of intestinal intraepithelial lymphocytes during acute rejection of small intestinal allografts

Infiltration of a transplanted organ by host lymphoid cells is the hallmark of acute rejection. However, after intestinal transplantation, physiological lymphocyte migration may lead to host cell infiltration of the graft even in the absence of rejection. It is unclear whether this lymphocyte migration also involves the intraepithelial compartment of the graft or whether infiltration there is indicative of acute rejection. We demonstrate here that host cell infiltration of the intestinal mucosa occurs both during acute rejection of a small bowel allograft and, to a lesser extent, when rejection is prevented by immunosuppression with FK506. The infiltrating host cells consisted of CD3 ⁺ T cells with a predominant CD4^–CD8 ⁺ phenotype resembling intraepithelial lymphocytes (IELs). Functional studies showed that the nonspecific cytolytic activity of IELs was not affected by acute rejection or by immunosuppression with FK506. These findings indicate that host cell infiltration of the intestinal mucosa does not connote an ongoing acute rejection. Furthermore, the decreased mucosal barrier function during acute rejection of intestinal allgrafts is probably not due to impaired cytolytic activity of IELs. Received: 10 March 1997 Received after revision: 6 November 1997 Accepted: 19 November 1997     

Antigen receptor-mediated B cell death is blacked by signaling via CD72 or treatment with dextran sukfate and is defective in autoimmunity-prone mice

Mature B cells undergo programmed cell death when surface(s)IGis extensively multimerized. A signal that blocks death of Bcells is thus required for activation of B cells in responseto antigen stimulation.Here we show that only a few diversetransmembranesignals capable of Inducing activation and proliferation ofB cell blocked sig-mediated death of normal mature B cells,fromdeath.The results suggest that a specific signal is requiredfor abrogating B cell death induced by sigcross-linking.Signalingvia IL-4 receptor and CD40, both of which are derived from activatedT cells, blocked sig-mediated death,as decribed previously.Signalingthrough a B cell antigen CD72,a counter-receptor of the pan-Tantigen CD4,also blocked death of anti-Ig-treated mouse spleenB cells.CD72 signalmay play a role in survival of B cells atthe initial step of T B interaction, where resting T cells recongnizeantigens such as llpopolyasccharide and dextran sulfate,andspleen B cells from New Zealand mice, which are prone to autoantibody-dependentautoimmune diseases,were resistant to required in antibody responseto freigin antigens regardless of T independence or T dependenceand in autoantibody production.     

Ex Vivo-Expanded Natural CD4+CD25+ Regulatory T Cells Synergize With Host T-Cell Depletion to Promote Long-Term Survival of Allografts

Foxp3⁺CD4⁺CD25⁺ natural regulatory T (nT_reg) cells have been shown in immunodeficient mice to suppress allograft rejection after adoptive cotransfer. We hypothesized that immunotherapy using ex vivo -expanded nT_reg could suppress allograft rejection in wild-type mice. Donor alloantigen (alloAg) specificity of naive splenic nT_reg was enriched in vitro by culturing with anti-CD3/CD28-coated Dynabeads plus bone marrow-derived dendritic cells (BM-DC) in the presence of interleukin (IL)-2 or IL-2 plus transforming growth factor (TGF)-β. On average, 96.2% fresh CD4⁺CD25⁺ nT_reg were intracellular Foxp3⁺. By d+20 in culture, 6.4% nT_reg were Foxp3⁺ following expansion with IL-2 alone, and 14.4% or 19.7% nT_reg were Foxp3⁺ when expanded with IL-2 plus 0.5 or 2.5 ng/mL TGF-β, respectively. In vitro , alloAg-enriched, TGF-β/IL-2-conditioned nT_reg exerted stronger donor alloAg-specific suppression than cells with IL-2 alone in mixed lymphocyte reaction (MLR) assays. In vivo , alloAg-enriched, TGF-β/IL-2-conditioned nT_reg expressed high-level Foxp3 following infusion, effectively overcame acute rejection and induced long-term survival of donor but not third-party heart allografts in peritransplant host T-cell-depleted mice. Long-term surviving allografts were noted to possess Foxp3⁺ graft-infiltrating cells of exogenous and endogenous origins. In conjunction with transient host T-cell depletion, therapeutic use of ex vivo -expanded nT_reg may be a practical means of preventing acute allograft rejection.     

Inhibition of a secondary human alloimmune response via the soluble active component of CD154 (CD40L) in severe combined immune-deficient mice engrafted with human lymphocytes

BACKGROUND: Alloimmunization requires a process known as co-stimulation. An important co-stimulatory pathway for most immune responses is mediated by the interaction of CD40 on antigen-presenting cells with CD154 (CD40L) on host T cells. Blockade of this co-stimulatory pathway simultaneous with exposure to challenge with HLA-incompatible cells is hypothesized to inhibit alloimmunization. STUDY DESIGN AND METHODS: Severe combined immune-deficient (SCID) mice were reconstituted with human peripheral blood lymphocytes (Hu-PBL-SCID mice) from a subject primed to HLA antigens and challenged with HLA-incompatible lymphocytes. Mice were challenged in the presence or absence of an 18-kDa soluble recombinant active form of human CD154 (18-kDa CD154). Human IgG production, alloimmunization, and in vitro T-cell responsiveness were assessed. RESULTS: There was no significant effect of 18-kDa CD154 on human IgG levels in these mice, but it inhibited the development of HLA-specific alloantibody in this model to five subsequent untreated white cell challenges. In vitro T-cell proliferation in a mixed lymphocyte culture was also prevented by 18-kDa CD154. CONCLUSION: The recombinant protein 18-kDa CD154 inhibited the ability of the Hu-PBL-SCID mice to mount a secondary immune response to allostimulation. This implies that transfusion-induced alloimmunization utilizes CD40-CD154 co-stimulation and that blockade of this pathway can inhibit T-cell function and interfere with the development of alloimmunization.