Oligomeric MHC molecules and their homologues: state of the art

This special issue of the Journal of Immunological Methods brings together articles from some of the leaders in labelling antigen-specific T and NKT cells, describing recent technical advances and their impact on the study of immunology. Although tetramers, or tetrameric MHC class I/peptide complexes, are the best known reagents in the field, various forms of oligomeric complexes are now being successfully used to detect antigen-specific T cells, including cytotoxic T lymphocytes, MHC class II-restricted CD4+ T cells, and glycolipid-specific T cells restricted by CD1 isoforms. The articles presented here detail the breadth of the oligomeric structures being used to probe T, NK and NKT cell function, and cover both the technical and practical aspects of their use, as well as the new biology revealed. In addition to providing a summary of the current state of the art, these contributions also provide clear pointers to strategies likely to succeed in the future. In this introductory chapter, we summarise the work presented in the other articles of this issue, and provide an overarching view of this rapidly evolving field. We also provide a summary of the MHC class I molecules successfully refolded to date, and provide references to other relevant sources of technical information.     

树突状细胞在黏膜免疫模型小鼠中的分布及E-cadherin和ICAM-1表达的研究

目的通过研究小鼠树突状细胞在黏膜免疫模型小鼠中分布特征及上皮型钙黏附分子（E-cadherin）和细胞间黏附分子-1（ICAM-1）的表达,以探讨E-cadherin和ICAM-1在树突状细胞迁移过程中的调控作用.方法采用光镜和免疫组织化学染色方法,观察黏膜免疫模型小鼠中树突状细胞的分布特征;分析E-cadherin和ICAM-1的表达情况.结果体内的树突状细胞在黏膜免疫模型小鼠中,主要分布于肠系膜淋巴结、回肠集合淋巴小结、胃和空回肠黏膜及黏膜下层,与对照组相比有显著差异,其ICAM-1表达明显增高,E-cadherin表达下调,分别与对照组数密度和面密度比较有显著差异.结论在树突状细胞迁移运动过程中,E-cadherin和ICAM-1黏附分子可能起着关键性的调控作用.     

Loss of claudin-1 expression induces epithelial-mesenchymal transition through nuclear factor-κB activation in colorectal cancer

Objective

The aim of this study was to elucidate the clinicopathological significance and prognostic role of loss of claudin-1 in colorectal cancer (CRC).

IMMUNOHISTOCHEMICAL DISTRIBUTION OF CANNABINOID CB 1 RECEPTOR IN THE RAT CENTRAL NERVOUS SYSTEM

IMMUNOHISTOCHEMICAL DISTRIBUTION OF CANNABINOID CB 1 RECEPTOR IN THE RAT CENTRAL NERVOUS SYSTEM@邹冈     

Susceptibility to clinically manifest cyclosporine A (CsA)-induced autoimmune disease is associated with interferon-gamma (IFN-γ)-producing CD45RC+RT6− T helper cells

Lethally irradiated Lewis (LEW) rats reconstituted with syngeneic bone marrow and given CsA for a 4-week period, develop, upon withdrawal of CsA, a graft-versus-host-like disease, so-called CsA-induced autoimmunity (CsA-AI). This T cell-mediated autoimmune disease is thymus-dependent; it is generally held that this disease is a consequence of aberrant T cell recovery brought about by CsA. In this study we determined mononuclear cell subsets phenotypically by tri-colour flow cytometry. A strong decrease in recent thymic emigrants (Thy1.1⁺, TCR αβ⁺) was observed as a consequence of CsA treatment, eventually resulting in decreased absolute peripheral T cell numbers. In these rats no altered CD4:CD8 T cell ratio was observed before onset of CsA-AI; CD4⁺ and CD8⁺ cells consisted predominantly of monocytes (CD4^dim+, TCR αβ⁻) and natural killer cells (CD8⁺, TCR αβ⁻), respectively. LEW rats, x-irradiated, syngeneic bone marrow-reconstituted and treated with CsA, showed a marked and persistent, relative expansion of mature CD45RC⁺, RT6⁻ Th cells. In contrast, Brown-Norway rats treated in a similar fashion, or LEW rats subjected to either CsA treatment or x-irradiation, did not show a comparable expansion of mature CD45RC⁺, RT6⁻ Th cells, nor did these animals develop CsA-AI. The CD45RC⁺, RT6⁻ Th cells produced IL-2, and moreover constituted the only Th subset producing IFN-γ upon stimulation, and therefore were considered as Th1-like effector cells. These results are consistent with the view that a persistent preponderance of Th1 cells and not the mere presence of autoreactive cells determines whether or not clinically manifest CsA-AI will occur.     

Antibodies to PAI-1 alter the invasive and migratory properties of human tumour cells in vitro

Recent reports suggest that elevated levels of plasminogen activator inhibitor-1 (PAI-1) may contribute to tumour progression. The studies reported here were designed to help elucidate PAI-1's contribution to the invasive and migratory phenotype. Antibodies to PAI-1 dose-dependently, and significantly, inhibited the invasive and migratory potential of human HT1080 fibrosarcoma cells, as did an antibody to uPA and the plasmin inhibitor aprotinin. Invasion of the human melanoma cell line, BLM, was also attenuated by the anti-PAI-1 monoclonal antibody MAI-12. The non-invasive human melanoma cell line, IF6, which does not express uPA, provided further confirmation of PAI-1 and uPA's role as, upon transfection with uPA, this cell line attained an invasive phenotype, which was again attenuated by MAI- 12. Although antibodies to PAI-1 did not affect the adhesion of HT1080 cells to vitronectin, the antibody to uPA reduced their attachment. Addition of exogenous PAI-1, however, prevented HT1080 cell adhesion (IC₅₀ 180nM) and promoted cell detachment from vitronectin. Furthermore melanoma cells transfected with a uPA variant, which had an impaired interaction with PAI-1, were not invasive and had impaired binding to vitronectin. These data highlight the importance of a balanced proteolysis and suggest an additional role for PAI-1 distinct from its role in proteolysis. These data also suggest that uPA and PAI-1 may co-operate in the migratory process by respectively facilitating the attachment to, and subsequent detachment from, vitronectin in the extracellular matrix. These results support the clinical findings and indicate that modulation of PAI-1 activity may be of therapeutic benefit for the treatment of cancer. This revised version was published online in July 2006 with corrections to the Cover Date.     

Iloprost对内皮细胞抗血栓功能的影响

以体外培养的猪主动脉内皮细胞（ＥＣ）为模型研究Ｉｌｏｐｏｓｔ对ＥＣ抗血栓功能的影响。用放免法、发色底物法测定培养液中６－酮－ＰＧＦ１α（６－ｋｅｔｏ－ＰＧＦ１α），血栓素Ｂ２（ＴＸＢ２）含量，纤溶酶原激活物（ＰＡ），纤溶酶原激活物抑制物（ＰＡＩ）活性及ＥＣ环磷酸腺苷（ｃＡＭＰ）含量。结果表明：Ｉｌｏｐｒｏｓｔ中以使ＥＣ生成６－ｋｅｔｏ－ＰＧＦ１α，ｃＡＭＰ含量显著增多，ＴＸＢ２含量显著减少，并使Ｐ     

Glucose preferences in wild and domestic guinea pigs

Male wild (Cavia aperea) and domestic (C. porcellus) guinea pigs were tested in two-bottle choice tests for preferences between glucose solutions of different concentrations and de-ionized water. Wild males showed significant preferences for concentrations between 0.025 and 0.4 M glucose while domestic males preferred only the 0.2 M glucose solution to de-ionized water. C. aperea males also consumed significantly greater volumes of liquid per kg body $\text{wt.}{}^{\mathrm{<mtext>3</mtext><mtext>4</mtext>}}$ during the glucose tests than did the C. porcellus males. These comparative results contrast sharply with those obtained by other authors with wild and domestic Norway rats.     

Benzylpenicillin preparations can evoke a systemic anaphylactic reaction in guinea pigs

All of the five commercially available benzylpenicillin preparations obtained from different sources and a PcG preparation prepared by filtration of a commercial PcG on Sephadex G10 elicited the systemic anaphylactic reactions in guinea pigs which had been immunized with benzylpenicilloyl (BPO)-Ascaris extract conjugate (BPO-As) mixed with aluminum hydroxide gel. These preparations could evoke no such reactions in guinea pigs immunized with BPO-bovine gamma globulin conjugate (BPO-BGG) emulsified with complete Freund's adjuvant. The severity of the systemic anaphylactic reactions correlated significantly with the titers of either 8-day passive cutaneous anaphylactic (8-day PCA) reactions or 4-hr PCA reactions evoked with the same benzylpenicillin preparations. In vitro benzylpenicillin preparation contracted the tracheas of the guinea pigs immunized with BPO-As. These results indicated that the commercially available benzylpenicillin preparations have enough antigenicity to evoke systemic anaphylactic reactions in guinea pigs immunized with BPO-As mixed with aluminum hydroxide gel. Such guinea pigs represent an animal model for investigation of penicillin allergy.