Therapeutic immunology最新文献_第4页

The regulation of lymphoid function during schistosomiasis: influence of T-cell-derived suppressor molecules on antigen recognition, cellular activation and granuloma formation. 血吸虫病期间淋巴功能的调节:t细胞源性抑制分子对抗原识别、细胞活化和肉芽肿形成的影响

Therapeutic immunology Pub Date : 1994-10-01

P J Perrin, R K Fidelus, K M Lee, S M Phillips

{"title":"The regulation of lymphoid function during schistosomiasis: influence of T-cell-derived suppressor molecules on antigen recognition, cellular activation and granuloma formation.","authors":"P J Perrin, R K Fidelus, K M Lee, S M Phillips","doi":"","DOIUrl":"","url":null,"abstract":"We have previously studied a T-cell derived soluble suppressor factor (TseF) which regulates immunopathology in schistosomiasis. The current studies address the mechanism whereby TseF suppresses the functional immune response in murine schistosomiasis. We assessed three stages of the immune response: (1) initial antigenic recognition using the criteria of antigen-mediated cell division or blast transformation (AMBT); (2) intracellular differentiation utilizing criteria of glutathione (GSH) and ornithine decarboxylase (ODC) production; and (3) efferent function utilizing criteria of in vitro granuloma formation (IVGF). We studied these three criteria of immune reactivity during the course of schistosomiasis. Lymphoid cells from acutely infected animals demonstrated high levels of antigen-mediated cell division and in vitro granuloma formation; ODC and GSH levels were low. Cells obtained from chronically infected animals demonstrated lower antigen-mediated cell division and granuloma formation; however, ODC and GHS levels were much higher, indicating that cells obtained from chronically infected animals are in a non-reactive state of increased activation. TseF strongly increased GSH and ODC levels in lymphocytes obtained from acutely infected animals, and this effect was augmented by the presence of antigen. However, TseF had minimal effects on initial antigenic recognition, and profoundly suppressed the effector function. The relationship between the effects of TseF on antigen recognition and function was regulated at the clonal level. TseF function required the generation of GSH. Since TseF is produced in chronic disease under conditions of decreased immunological reactivity, the alterations of GSH and ODC activity, induced by TseF, may be responsible for the regulation of immunopathology.","PeriodicalId":23039,"journal":{"name":"Therapeutic immunology","volume":"1 5","pages":"257-67"},"PeriodicalIF":0.0,"publicationDate":"1994-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18588928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Anti-CD4 activity of normal human immunoglobulin G for therapeutic use. (Intravenous immunoglobulin, IVIg). 治疗用正常人免疫球蛋白G抗cd4活性。静脉注射免疫球蛋白。

Therapeutic immunology Pub Date : 1994-10-01

V Hurez, S V Kaveri, A Mouhoub, G Dietrich, J C Mani, D Klatzmann, M D Kazatchkine

引用次数: 0

Evaluation of Fc gamma receptor mediated T-cell activation by two purified CD3 x CD19 bispecific monoclonal antibodies with hybrid Fc domains. 两种具有杂化Fc结构域的纯化CD3 x CD19双特异性单克隆抗体对Fc γ受体介导的t细胞活化的评价。

Therapeutic immunology Pub Date : 1994-10-01

I A Haagen, A J Geerars, E J Bast, G C de Gast, J G van de Winkel, W B de Lau

{"title":"Evaluation of Fc gamma receptor mediated T-cell activation by two purified CD3 x CD19 bispecific monoclonal antibodies with hybrid Fc domains.","authors":"I A Haagen, A J Geerars, E J Bast, G C de Gast, J G van de Winkel, W B de Lau","doi":"","DOIUrl":"","url":null,"abstract":"Two bispecific monoclonal antibodies (BsAb), differing in H chain isotype combination, were made for treatment of B-cell leukaemia/lymphoma; QAI-2, CD3-mouse-IgG1 x CD19-mouse-IgG2a and QAI-3, CD3-mouse-IgG1 x CD19-mouse-IgG2b. Both purified BsAb proved equally effective for their ability to target pre-activated T cells towards CD19 positive tumour cells. In T-cell proliferation assays, the capacity of Fc gamma RIa (CD64), Fc gamma RIIa-R131 and Fc gamma RIIa-H131 (CD32) transfected fibroblasts was tested to present the BsAb. The BsAb combining mouse (m) IgG1 and mIgG2a promoted T-cell activation in combination with the Fc gamma RIa transfectant; the mIgG1-mIgG2b BsAb was only marginally active. Both BsAb could not induce T-cell activation when presented by either of the Fc gamma RIIa transfectants. Similar results were obtained using PBMC cultures, containing Fc gamma RIa+/Fc gamma RIIa+ monocytes as accessory cells. The importance of Fc gamma R-dependent BsAb-mediated T-cell activation emerged from experiments with T cells and CD19 positive B-cell lines, showing that cross-linking via CD19+ target cells alone did not induce T-cell proliferation. Therefore, BsAb with functionally different Fc domains represent alternative strategies in BsAb therapy, the efficacy of which deserves to be compared in vivo.","PeriodicalId":23039,"journal":{"name":"Therapeutic immunology","volume":"1 5","pages":"279-87"},"PeriodicalIF":0.0,"publicationDate":"1994-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18588930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Engineering multiple-domain forms of the therapeutic antibody CAMPATH-1H: effects on complement lysis. 工程治疗性抗体campaign - 1h的多结构域形式:对补体裂解的影响。

Therapeutic immunology Pub Date : 1994-10-01

J Greenwood, S D Gorman, E G Routledge, I S Lloyd, H Waldmann

{"title":"Engineering multiple-domain forms of the therapeutic antibody CAMPATH-1H: effects on complement lysis.","authors":"J Greenwood, S D Gorman, E G Routledge, I S Lloyd, H Waldmann","doi":"","DOIUrl":"","url":null,"abstract":"Antibody-mediated lysis of cells involves a complex interaction between the cell, the target antigen, the antibody and host effector mechanisms. One such mechanism, complement-mediated cell lysis, requires the interaction of C1q with the antibody heavy chain constant regions, and in particular the CH2 domain. Here we investigate the potential benefit of multiple-domain forms of the therapeutic monoclonal antibody CAMPATH-1H. This antibody is directed against the CDw52 antigen expressed by human lymphocytes and has proven lytic abilities both in vitro and in vivo. Using target cells with either high or low antigen density, engineered antibodies that contained additional domains in tandem (CH2, hinge-CH2 or Fc intramolecular repeats) showed no improvement in complement-mediated lysis when compared with controls. However, a homodimeric form of the antibody that was engineered by mutation of a serine residue to cysteine near the carboxy-terminal of the CH3 domain, exhibited markedly improved lysis using target cells expressing antigen at low density. Interestingly, no improvement was seen using cells expressing antigen at high density. These results suggest that dimeric forms of antibodies could be useful for converting cells with low density antigens into useful targets for therapy.","PeriodicalId":23039,"journal":{"name":"Therapeutic immunology","volume":"1 5","pages":"247-55"},"PeriodicalIF":0.0,"publicationDate":"1994-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18590286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Degradation of ricin A chain by endosomal and lysosomal enzymes--the protective role of ricin B chain. 内体酶和溶酶体酶降解蓖麻毒素A链——蓖麻毒素B链的保护作用。

Therapeutic immunology Pub Date : 1994-08-01

A Bilge, J Howell-Clark, S Ramakrishnan, O W Press

{"title":"Degradation of ricin A chain by endosomal and lysosomal enzymes--the protective role of ricin B chain.","authors":"A Bilge, J Howell-Clark, S Ramakrishnan, O W Press","doi":"","DOIUrl":"","url":null,"abstract":"We investigated the role of intracellular processing of ricin A chain (RTA) by proteolytic enzymes on the expression of its ribosome inhibitory activity. Endosomal and lysosomal proteases extracted from Jurkat cells and purified cathepsins B, D and G were incubated with RTA, resulting in generation of a 28-kDa fragment by proteolytic cleavage. This process was reminiscent of the nicking of Pseudomonas exotoxin and Diphtheria toxin by intracellular proteases to produce functionally active toxin fragments. However, the ribosome inhibitory activity of the purified 28-kDa fragment of RTA was 11,000-fold less than that of native RTA, suggesting that such cleavage is not an essential step in the cytotoxic activity of the toxin. Addition of ricin B chain (RTB) in degradation assays resulted in the protection of RTA from proteolytic activities of lysosomes and cathepsins. However, RTB did not protect another RNA acting protein, RNAase; nor did excess amounts of unlabeled RTA or IgG protect labelled RTA from degradation, suggesting that the protective effect of RTB was specific to its interaction with RTA. Such a protective role for RTB may partially account for the higher toxicity of immunotoxins (ITs) containing whole ricin compared to ITs containing only RTA.","PeriodicalId":23039,"journal":{"name":"Therapeutic immunology","volume":"1 4","pages":"197-204"},"PeriodicalIF":0.0,"publicationDate":"1994-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18590282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The CD28 costimulatory pathway. CD28共刺激途径。

Therapeutic immunology Pub Date : 1994-08-01

H T Leung, P S Linsley

引用次数: 0

Chemokines, inflammation and the immune system. 趋化因子，炎症和免疫系统。

Therapeutic immunology Pub Date : 1994-08-01

D D Taub, J J Oppenheim

{"title":"Chemokines, inflammation and the immune system.","authors":"D D Taub, J J Oppenheim","doi":"","DOIUrl":"","url":null,"abstract":"The chemokine superfamily comprise two families of small secreted proteins that, with the exception of RANTES, beta-TG, and PF-4, are not expressed in resting cells but are rapidly induced in response to various inflammatory and mitogenic stimuli. These proteins function as chemoattractants and activating agents for inflammatory cells. At present, it appears that each of the chemokines have some activities that are unique and many that are overlapping. Important areas that still need to be unravelled are the signal transduction pathways that lead to induction of these genes and the identification of the serpentine receptors and signal transduction pathways that are activated by these proteins. alpha and beta chemokines are implicated as major participants in acute as well as chronic inflammatory reactions, inhibition of haematopoeisis, modulation of angiogenesis, and fibroplasia. Chemokines that act on T lymphocytes presumably influence the recruitment of immunocompetent cells to inflammatory sites. Although there is no evidence that chemokines play a role in the induction of immune reactions, they undoubtedly promote the effector limb of immunity. The likely possibility that chemokines may also contribute to the normal homing and distribution of leukocytes also needs to be evaluated. Although chemokines obviously have major differentiative effects on the functions of target cells, the possibility that they act as costimulants of cell growth also needs more study. Finally, chemokines are attractive targets for the development of new therapeutic agents. Inhibition of their activities may be an effective anti-inflammatory strategy; promoting their activity might enhance wound healing and tissue repair.","PeriodicalId":23039,"journal":{"name":"Therapeutic immunology","volume":"1 4","pages":"229-46"},"PeriodicalIF":0.0,"publicationDate":"1994-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18590285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The effects of an immunomodulatory LFA3-IgG1 fusion protein on nonhuman primates. 免疫调节LFA3-IgG1融合蛋白对非人灵长类动物的影响。

Therapeutic immunology Pub Date : 1994-08-01

P L Chisholm, C A Williams, W E Jones, G R Majeau, F B Oleson, B Burrus-Fischer, W Meier, P S Hochman

引用次数: 0

Interleukin-12: a cytokine with therapeutic potential in oncology and infectious diseases. 白细胞介素-12:一种在肿瘤和传染病中具有治疗潜力的细胞因子。

Therapeutic immunology Pub Date : 1994-06-01

M K Gately, U Gubler, M J Brunda, R R Nadeau, T D Anderson, J M Lipman, U Sarmiento

引用次数: 0

Interleukin-10 and its receptor. 白细胞介素-10及其受体。

Therapeutic immunology Pub Date : 1994-06-01

A S Ho, K W Moore

引用次数: 0