Allorecognition of human neural stem cells by peripheral blood lymphocytes despite low expression of MHC molecules: role of TGF-beta in modulating proliferation.


:Neural stem cells (NSCs) transplantation has been proposed as a means of restoring damaged brain tissue, a possibility rendered more likely by reports of low NSCs immunogenicity in various experimental models because of low expression of MHC class I and II as well as co-stimulatory molecules. We investigated the immunogenicity of a human NSC line grown in normal culture conditions and in the presence of pro-inflammatory cytokines IFN-gamma and tumor necrosis factor alpha by one-way mixed lymphocyte reaction (MLR) experiments with peripheral blood lymphocytes from eight HLA-incompatible donors. NSCs stimulated lymphocyte proliferation in almost all donors tested, with stimulation indices in the range of the low-end distribution curve of MLR between donors. The healthy subject that gave negative MLR results was the best compatible donor with respect to NSC haplotype. Since we observed low MLR responses overall, we studied if NSCs might exert any immunomodulatory activity. We detected transcription and release of the immunomodulatory molecule transforming growth factor beta (TGF-beta)-1; moreover, the addition of TGF-beta1 in MLR experiments down-regulated proliferative responses. To further confirm the immunological potential of human NSCs, we studied xenogeneic recognition of NSCs by immunocompetent cells derived from C57BL/6 mice, showing that NSCs can elicit an allo(xeno) response ex vivo. Our data indicate that NSCs have low but not negligible immunogenic potential that is sufficient to activate peripheral lymphocytes. Secretion of TGF-beta1 might balance the immunogenicity of NSCs. Nevertheless, the possibility that allo-NSCs grafting might induce in the long term an immune activation, thus vanishing their therapeutical effect, should not be overlooked and deserves further investigation.


Int Immunol


International immunology


Ubiali F,Nava S,Nessi V,Frigerio S,Parati E,Bernasconi P,Mantegazza R,Baggi F




Has Abstract


2007-09-01 00:00:00














  • A quantitative model for neutrophil response and delayed-type hypersensitivity reaction in rats orally inoculated with various doses of Salmonella Enteritidis.

    abstract::Our aim was to investigate the quantitative relationship between inoculation doses and physiological responses to infection by Salmonella enterica serovar Enteritidis. Rats were orally inoculated with 10-10(9) c.f.u. of S. Enteritidis and monitored for 6 days. Neutrophil and delayed-type hypersensitivity (DTH) respons...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Takumi K,Garssen J,Havelaar A

    更新日期:2002-02-01 00:00:00

  • Molecular cloning of cDNA encoding MS2 antigen, a novel cell surface antigen strongly expressed in murine monocytic lineage.

    abstract::cDNA clones which strongly hybridized with a 3.1 kb mRNA from mouse macrophages and macrophage cell lines and weakly with mRNA from P815 but not from a variety of other cell lines and tissues were isolated from cDNA libraries constructed using mRNA from murine macrophage cell lines and peritoneal macrophages. Treatmen...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Yoshida S,Setoguchi M,Higuchi Y,Akizuki S,Yamamoto S

    更新日期:1990-01-01 00:00:00

  • Selective IgG2 deficiency due to a point mutation causing abnormal splicing of the Cgamma2 gene.

    abstract::The mechanism underlying selective IgG subclass deficiency is largely unknown in humans. We have previously reported the acquisition of a complete IgG2 deficiency in a leukemia patient after bone marrow transplantation. Southern blot analysis showed a deletion including the Cgamma2 and Cgamma4 genes on one chromosome ...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Zhao Y,Pan-Hammarström Q,Zhao Z,Wen S,Hammarström L

    更新日期:2005-01-01 00:00:00

  • Developmental control of antigen-induced thymic transcription factors.

    abstract::Antigen engagement of the TCR may lead to activation of mature T cells while inducing deletion or positive selection of immature thymocytes. Using thymocytes from TCR transgenic mice recognizing the allo-antigen H-2Kb we investigated whether double-positive CD4+CD8+ (DP) thymocytes constitute a particular developmenta...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Simon AK,Auphan N,Schmitt-Verhulst AM

    更新日期:1996-09-01 00:00:00

  • A subcutaneously injected UV-inactivated SARS coronavirus vaccine elicits systemic humoral immunity in mice.

    abstract::The recent emergence of severe acute respiratory syndrome (SARS) was caused by a novel coronavirus, SARS-CoV. It spread rapidly to many countries and developing a SARS vaccine is now urgently required. In order to study the immunogenicity of UV-inactivated purified SARS-CoV virion as a vaccine candidate, we subcutaneo...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Takasuka N,Fujii H,Takahashi Y,Kasai M,Morikawa S,Itamura S,Ishii K,Sakaguchi M,Ohnishi K,Ohshima M,Hashimoto S,Odagiri T,Tashiro M,Yoshikura H,Takemori T,Tsunetsugu-Yokota Y

    更新日期:2004-10-01 00:00:00

  • Human CD8 co-receptor is strictly involved in MHC-peptide tetramer-TCR binding and T cell activation.

    abstract::Although there has been extensive analysis on the capacity of MHC-peptide tetramers to bind antigen-specific TCR, there have been comparatively few studies regarding the role of the CD4 and CD8 co-receptors in binding and activation by these multimeric molecules. Here, we start from the observation that different anti...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Campanelli R,Palermo B,Garbelli S,Mantovani S,Lucchi P,Necker A,Lantelme E,Giachino C

    更新日期:2002-01-01 00:00:00

  • Expression of CD45 isoforms by fresh and activated human gamma delta T lymphocytes and natural killer cells.

    abstract::Naive and primed alpha beta T cells can be distinguished on the basis of their differential expression of CD45RA and CD45RO, respectively. The present study indicates that these CD45-isoforms also identify naive and primed maturational stages of gamma delta T cells and natural killer (NK) cells. In peripheral blood, a...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Braakman E,Sturm E,Vijverberg K,van Krimpen BA,Gratama JW,Bolhuis RL

    更新日期:1991-07-01 00:00:00

  • p40 molecule regulates NK cell activation mediated by NK receptors for HLA class I antigens and TCR-mediated triggering of T lymphocytes.

    abstract::p40 was previously described as a regulatory molecule capable of inhibiting both the natural and the CD16-mediated cytotoxicity of NK cells. In this study, we analyze the effect of p40 molecule engagement on the NK cell triggering induced by activating HLA class I-specific NK receptors (NKR) or on TCR alpha beta-media...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Poggi A,Tomasello E,Revello V,Nanni L,Costa P,Moretta L

    更新日期:1997-09-01 00:00:00

  • Human MD-2 confers on mouse Toll-like receptor 4 species-specific lipopolysaccharide recognition.

    abstract::Toll-like receptor 4 (TLR4) recognizes lipopolysaccharide (LPS). MD-2 is associated with TLR4 and imparts LPS responsiveness to it. Little is known, however, as to whether MD-2 directly regulates LPS recognition by TLR4. To address the issue, we took advantage of a species-specific pharmacology of lipid IVa, an analog...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Akashi S,Nagai Y,Ogata H,Oikawa M,Fukase K,Kusumoto S,Kawasaki K,Nishijima M,Hayashi S,Kimoto M,Miyake K

    更新日期:2001-12-01 00:00:00

  • CD86 (B70/B7-2) on endothelial cells co-stimulates allogeneic CD4+ T cells.

    abstract::In vascularized organ transplantation, vascular endothelial cells (EC) confronting recipient T cells are potentially significant APC initiating cellular immune responses that lead to rejection. In the present study, we studied the ability of human EC to stimulate allogeneic T cells and the co-stimulatory molecules inv...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Seino K,Azuma M,Bashuda H,Fukao K,Yagita H,Okumura K

    更新日期:1995-08-01 00:00:00

  • Calcitonin gene-related peptide enhances experimental autoimmune encephalomyelitis by promoting Th17-cell functions.

    abstract::T(h)17 cells, an inflammatory T helper cell subset, are involved in the pathogenesis of various inflammatory, autoimmune and allergic diseases. Recent evidence supports the idea that immune cell functions and the inflammatory response are finely regulated by various physiological substances. Calcitonin gene-related pe...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Mikami N,Watanabe K,Hashimoto N,Miyagi Y,Sueda K,Fukada S,Yamamoto H,Tsujikawa K

    更新日期:2012-11-01 00:00:00

  • In vitro immunization of naive mouse B cells: establishment of IgM secreting hybridomas specific for souble protein or hapten from B cells cultured on CD40 ligand transfected mouse fibroblasts.

    abstract::CD40 has been shown to play an important role in the regulation of B cell survival, proliferation and Ig class switching. The natural partner for CD40 is CD40 ligand, gp 39, which is transiently expressed on activated T cells. In vitro, CD40 ligation leads to polyclonal B cell proliferation and, in the presence of app...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Wohlleben G,Gray D,Schimpl A

    更新日期:1996-03-01 00:00:00

  • Characterization of dendritic-like cells derived from t(9;22) acute lymphoblastic leukemia blasts.

    abstract::We asked herein whether functional dendritic-like cells could be generated from t(9;22) acute lymphoblastic leukemia (ALL) blasts. We first determined that the combination of interleukin (IL)-1beta, IL-3, IL-7, tumor necrosis factor-alpha, stem cell factor and CD40 ligand was optimal for generating dendritic-like cell...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Lee J,Sait SN,Wetzler M

    更新日期:2004-10-01 00:00:00

  • Loss of SDF-1 receptor expression during positive selection in the thymus.

    abstract::SDF-1 is a member of the CXC chemokines. In contrast to other chemokines that are induced by inflammation, SDF-1 is constitutively produced by stromal cells. In order to investigate the physiological roles of SDF-1, we constructed a fusion protein, SDF-1-Cgamma1, composed from murine SDF-1alpha and the constant region...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Suzuki G,Nakata Y,Dan Y,Uzawa A,Nakagawa K,Saito T,Mita K,Shirasawa T

    更新日期:1998-08-01 00:00:00

  • Administration of IL-12 during ongoing immune responses fails to permanently suppress and can even enhance the synthesis of antigen-specific IgE.

    abstract::The synthesis of antibodies of the IgE isotype in mice largely depends on IL-4, a cytokine that is released by T lymphocytes of the Th2 subtype. IL-12 is a cytokine considered to direct Th cell development into a Th1 direction and to suppress Th2 responses including the synthesis of IgE. Here we report about the influ...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Germann T,Guckes S,Bongartz M,Dlugonska H,Schmitt E,Kolbe L,Kölsch E,Podlaski FJ,Gately MK,Rüde E

    更新日期:1995-10-01 00:00:00

  • A three-dimensional model of the Fas/APO-1 molecule: cross-reactivity of anti-Fas antibodies explained by structural mimicry of antigenic sites.

    abstract::Fas/APO-1 is a member of the tumor necrosis factor (TNF)/nerve growth factor receptor family. This cell surface protein, when associated with the Fas/APO-1 ligand or specific mAb, elicits an apoptotic response in susceptible cells via an oligomerization of its intracellular domains, termed the'death domains'. We have ...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Fadeel B,Lindberg J,Achour A,Chiodi F

    更新日期:1998-02-01 00:00:00

  • Vaccination of the Leishmania major susceptible BALB/c mouse. I. The precise selection of peptide determinant influences CD4+ T cell subset expression.

    abstract::BALB/c mice are susceptible to cutaneous leishmaniasis upon infection with Leishmania major while C57BL/6 are not. There is a major promastigote surface protease (PSP or gp63) which is available in both native and recombinant forms, and for which the primary amino acid sequence is known. Immunization with PSP has been...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Soares LR,Sercarz EE,Miller A

    更新日期:1994-05-01 00:00:00

  • On the mechanism of human T cell suppression.

    abstract::Previous evidence from several laboratories suggests that CD8+ T suppressor cells may be important regulatory elements governing specific unresponsiveness of lepromatous lepromatous leprosy patients to M.leprae. To analyse the mechanism of suppression, CD8+ Ts clones were established from lesions and peripheral blood ...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Salgame P,Modlin R,Bloom BR

    更新日期:1989-01-01 00:00:00

  • The lineage relationship between virgin and memory B cells.

    abstract::J11d is expressed on a variety of hemopoietic cells, including B cells. In previous studies, we have shown that B cells are heterogeneous with respect to their levels of J11d expression and that memory B cells are contained within the J11dlo B cell population. In this report, we have further examined the relationship ...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Yin XM,Vitetta ES

    更新日期:1992-06-01 00:00:00

  • Natural peptide ligand motifs of two HLA molecules associated with myasthenia gravis.

    abstract::The peptide motifs of two HLA molecules, B8 and DR3(17), which are associated with autoimmune diseases including myasthenia gravis, were determined from natural peptide pools using Edman degradation. The majority of HLA-B8 ligands are nonamers preferentially terminated by leucine. As a characteristic feature of the HL...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Malcherek G,Falk K,Rötzschke O,Rammensee HG,Stevanović S,Gnau V,Jung G,Melms A

    更新日期:1993-10-01 00:00:00

  • Activation of mast cells by incorporation of cholesterol into rafts.

    abstract::IgE plus antigen-stimulated mast cells degranulate, synthesize leukotrienes and secrete cytokines. According to the coalescence model this process is initiated in specific membrane compartments termed rafts. There, enhanced levels of glycosphingolipids and cholesterol stabilize the interaction of FcepsilonRI and Lyn, ...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Baumruker T,Csonga R,Pursch E,Pfeffer A,Urtz N,Sutton S,Bofill-Cardona E,Cooke M,Prieschl E

    更新日期:2003-10-01 00:00:00

  • Skewed V beta TCR repertoire of CD8+ T cells in murine Trypanosoma cruzi infection.

    abstract::We have followed CD4 and CD8 TCR V beta repertoires during the acute phase of Trypanosoma cruzi infection in a resistant mouse strain (C57BL/6). No major changes were found in the V beta TCR distributions analyzed (covering roughly 40% of the TCR repertoire) in peripheral CD4 T lymphocytes, confirming the polyclonal n...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Leite-de-Moraes MC,Coutinho A,Hontebeyrie-Joskowicz M,Minoprio P,Eisen H,Bandeira A

    更新日期:1994-03-01 00:00:00

  • Basophils as T(h)2-inducing antigen-presenting cells.

    abstract::Recent studies have revealed a role for basophils as antigen-presenting cells that preferentially induce T(h)2 cells in response to complexes of antigen plus antigen-specific IgE, to protease allergens or to helminthic parasites in vitro and in vivo through the production of 'early IL-4' and the presentation to CD4(+)...

    journal_title:International immunology

    pub_type: 杂志文章,评审


    authors: Yoshimoto T

    更新日期:2010-07-01 00:00:00

  • Maintenance of clonal anergy by endogenously produced IL-10.

    abstract::Inadequate co-stimulation of tumor reactive T cells may contribute to the fact that antigenic tumors are not normally rejected by the immune system. We recently reported that the induction of profound unresponsiveness in a T cell clone by melanoma cells expressing MHC class II antigens may provide a mechanism for thes...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Becker JC,Czerny C,Bröcker EB

    更新日期:1994-10-01 00:00:00

  • TLR2 as an essential molecule for protective immunity against Toxoplasma gondii infection.

    abstract::To investigate the role of the Toll-like receptor (TLR) family in host defense against Toxoplasma gondii, we infected TLR2-, TLR4- and MyD88-deficient mice with the avirulent cyst-forming Fukaya strain of T. gondii. All TLR2- and MyD88-deficient mice died within 8 days, whereas all TLR4-deficient and wild-type mice su...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Mun HS,Aosai F,Norose K,Chen M,Piao LX,Takeuchi O,Akira S,Ishikura H,Yano A

    更新日期:2003-09-01 00:00:00

  • Mechanisms of acute inflammatory lung injury induced by abdominal sepsis.

    abstract::Sequestration of neutrophils and release of histotoxic mediators are considered important for the development of pathologic alterations of the lung defined as adult respiratory distress syndrome. Mechanisms of inflammatory lung injury caused by abdominal sepsis were investigated using the colon ascendens stent periton...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Neumann B,Zantl N,Veihelmann A,Emmanuilidis K,Pfeffer K,Heidecke CD,Holzmann B

    更新日期:1999-02-01 00:00:00

  • A 3-D model for the CD40 ligand predicts that it is a compact trimer similar to the tumor necrosis factors.

    abstract::Based on the similarity in primary structure between the newly characterized ligand for CD40 (CD40L) and the tumor necrosis factors (TNFs), we have modeled a detailed 3-D structure for CD40L. We used the known structure of TNF alpha as a template for the generation of the CD40L model. The soundness of the model-buildi...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Peitsch MC,Jongeneel CV

    更新日期:1993-02-01 00:00:00

  • TCR-mediated activation promotes GITR upregulation in T cells and resistance to glucocorticoid-induced death.

    abstract::T lymphocytes (pivotal in many inflammatory pathologies) are targets for glucocorticoid hormone (GC). How TCR-mediated activation and GC signaling via glucocorticoid receptor (GR) impact on T-cell fates is not fully defined. We delineated here the expression of a recently identified glucocorticoid-induced TNF receptor...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Zhan Y,Funda DP,Every AL,Fundova P,Purton JF,Liddicoat DR,Cole TJ,Godfrey DI,Brady JL,Mannering SI,Harrison LC,Lew AM

    更新日期:2004-09-01 00:00:00

  • Transendothelial migration of effector T cells across inflamed endothelial barriers does not require heparan sulfate proteoglycans.

    abstract::Leukocyte diapedesis is a chemotactic multistep process that requires optimal chemoattractant presentation by the endothelial barrier. Recent studies have described a critical role for heparan sulfate glycosaminoglycans (HSGAGs) in the presentation and functions of chemokines essential for lymphocyte interactions with...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Stoler-Barak L,Barzilai S,Zauberman A,Alon R

    更新日期:2014-06-01 00:00:00

  • IgE repertoire and immunological memory: compartmental regulation and antibody function.

    abstract::It is now generally recognized that bone marrow is the survival niche for antigen-specific plasma cells with long-term immunological memory. These cells release antibodies into the circulation, needed to prime effector cells in the secondary immune response. These antibodies participate in the surveillance for antigen...

    journal_title:International immunology

    pub_type: 杂志文章,评审


    authors: Gould HJ,Wu YB

    更新日期:2018-08-30 00:00:00