Abstract:
:The co-existence of tumor specific immunity with a progressing tumor is observed in a variety of experimental systems and remains one of the major paradoxes of tumor immunology. We now report that a human melanoma cell line (SMC) expressing MHC class II was able to induce clonal anergy in a specific, MHC-restricted CD4+ T cell clone (STC3). Clonal anergy is a mechanism of T lymphocyte tolerance induced by antigen receptor stimulation in the absence of co-stimulation. We observed that a CD4+ T cell clone and an autologous melanoma cell line form conjugates with each other that leads to an increase of [Ca++]i in the T cell clone; however, this interaction failed to induce IL-2 production or proliferation of the T cell clone. Furthermore, this interaction rendered this T cell clone unresponsive to subsequent stimulation. All these effects were MHC class II restricted. Therefore, the human melanoma cell line SMC was capable of delivering antigen-specific signals to the T cell clone, but did not deliver the co-stimulatory signals, e.g. a B7/CD28 interaction, necessary for full T cell activation. Transfection of the melanoma cells with an expression vector containing a B7 cDNA that resulted in subsequent expression of B7 on its cell surface rendered it into a fully competent antigen presenting cell, which is able to induce a nuclear factor binding to the IL-2 promoter in the specific T cell clone resulting in enhanced IL-2 transcription, synthesis, and T cell proliferation. These findings suggest that manipulation of co-stimulation may offer new strategies for future tumor immunotherapy.
journal_name
Int Immunoljournal_title
International immunologyauthors
Becker JC,Brabletz T,Czerny C,Termeer C,Bröcker EBdoi
10.1093/intimm/5.12.1501subject
Has Abstractpub_date
1993-12-01 00:00:00pages
1501-8issue
12eissn
0953-8178issn
1460-2377journal_volume
5pub_type
杂志文章abstract::The human chymase (HC) is a major granule constituent of mast cells (MCs) residing in the connective tissue and the sub-mucosa. Although many potential substrates have been described for this important MC enzyme, its full range of in vivo substrates has most likely not yet been identified. A major step toward a better...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxn128
更新日期:2009-01-01 00:00:00
abstract::In contrast to most organs, the anatomy of the liver may allow naive CD8(+) T cells to make direct contact with liver parenchymal cells. We have previously shown, using a combination of TCR transgenic T cells specific for H-2 K(b) and hepatocytes expressing a transgenic H-2 K(b) molecule, that hepatocytes can induce a...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/11.8.1225
更新日期:1999-08-01 00:00:00
abstract::Autoimmune gastritis is a CD4+ T cell-mediated disease induced in genetically susceptible mice by thymectomy on the third day after birth. Previous linkage analysis indicated that Gasa1 and Gasa2, the major susceptibility loci for gastritis, are located on mouse chromosome 4. Here we verified these linkage data by sho...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxm087
更新日期:2007-09-01 00:00:00
abstract::EBV-encoded latent membrane protein 1 (LMP1) is critical for EBV-driven B-cell transformation and most EBV-associated malignancies and is also implicated in exacerbation of autoimmunity. LMP1 functionally mimics the TNFR superfamily member CD40, but LMP1-induced signals and downstream B-cell functions are amplified an...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxt052
更新日期:2014-03-01 00:00:00
abstract::Previously we examined the ability of the host's immune responses to regulate Ig production in an IgE-secreting murine plasma cell tumor (B53). In the present study we have examined the reverse phenomenon, in that we have investigated the effects of this and other plasma cell tumors on the immune responses of their ho...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/7.7.1029
更新日期:1995-07-01 00:00:00
abstract::The immunomodulator FTY720 inhibits lymph node (LN) and thymic egress, thereby constraining T cell circulation and reducing peripheral T cell numbers. Here, we analyzed in mouse models the as yet scarcely characterized impact of long-term (up to 6 months) FTY720 exposure on T cell homeostasis and possible consequences...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxn023
更新日期:2008-05-01 00:00:00
abstract::Germline CH transcripts initiate from a non-coding I exon and terminate downstream of the associated CH exons. Ig heavy chain class switch recombination from the VDJ-C mu gene to particular downstream CH genes appears to be regulated by a process that involves mitogen and/or cytokine induction of germline CH transcrip...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/6.4.491
更新日期:1994-04-01 00:00:00
abstract::Semaphorin 3A (Sema3A), originally identified as a potent growth cone collapsing factor in developing sensory neurons, is now recognized as a key player in immune, cardiovascular, bone metabolism and neurological systems. Here we established an anti-Sema3A monoclonal antibody that neutralizes the effects of Sema3A bot...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxv014
更新日期:2015-09-01 00:00:00
abstract::Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired type hemolytic disorder. Hematopoietic cells of patients with PNH are deficient in glycosylphosphatidylinositol (GPI) anchored membrane proteins. Since some membrane-bound complement inhibitors, such as CD59 and decay accelerating factor (DAF), are GPI anchored ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/4.11.1263
更新日期:1992-11-01 00:00:00
abstract::NK cells were first identified in 1975 and represent the prototypical group 1 innate lymphoid cell (ILC). More recently, the discovery of new members of the ILC family has highlighted the complexity of this innate lymphoid lineage. Importantly, it has been recognized that different subsets exist within the group 1 ILC...
journal_title:International immunology
pub_type: 杂志文章,评审
doi:10.1093/intimm/dxv051
更新日期:2016-01-01 00:00:00
abstract::Interleukin-15 (IL-15) is a cytokine critical for maintenance of intestinal intra-epithelial lymphocytes (IELs), especially CD8αα + IELs (CD8αα IELs). In the intestine, IL-15 is produced by intestinal epithelial cells (IECs), blood vascular endothelial cells (BECs) and hematopoietic cells. However, the precise role of...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxz082
更新日期:2020-05-08 00:00:00
abstract::Apoptosis is a major mechanism whereby HIV-1 depletes uninfected CD4+ and CD8+ T cells. We previously showed that resting peripheral blood T cells derived from healthy donors were killed by an apoptotic mechanism after adsorption to gp120-containing, protease-defective HIV-1 (L-2) particles, more effectively than pare...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/9.10.1453
更新日期:1997-10-01 00:00:00
abstract::IL-7 is a required factor for T-cell homeostasis. Because of low expression levels and poor reagent availability, the cellular sources of IL-7 have proven challenging to characterize. In this study, we describe a reporter mouse in which enhanced GFP is expressed from the endogenous Il7 locus. We show that IL-7 is prod...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxt012
更新日期:2013-08-01 00:00:00
abstract::Epitope spreading has been best characterized as an exacerbating factor in CD4(+) T cell-dependent autoimmune disease models and is believed to occur via presentation of antigens liberated by tissue destruction initiated by CD4(+) T cells specific for a primary epitope. The growing evidence that exogenous antigens can...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/13.5.625
更新日期:2001-05-01 00:00:00
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
doi:10.1093/intimm/4.6.691
更新日期:1992-06-01 00:00:00
abstract::Using anti-Tac (anti-alpha chain) and 2R-B (anti-beta chain) antibodies, we studied the roles of IL-2 receptor subunits (alpha and beta chains) in the formation of IL-2 and high-affinity IL-2 receptor complex, which is the initial event of IL-2 induced T cell growth. High-affinity IL-2 binding which was undetectable i...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/2.6.521
更新日期:1990-01-01 00:00:00
abstract::BALB.xid mice, carrying an X-linked mutation leading to the absence of CD5+ B cells, are highly resistant to Trypanosoma cruzi infection. These mice clear blood parasites in the acute phase of infection and do not develop the inflammatory infiltration characteristically observed in the chronic phase of susceptible str...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/8.8.1213
更新日期:1996-08-01 00:00:00
abstract::The alternative complement pathway (ACP) in vertebrates is known to be important in inflammatory reactions, and to be activated by foreign substances such as bacterial lipopolysaccharide (LPS) and zymosan, although to date no intrinsic activators have been identified except complement receptor type 2. From the point o...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/5.10.1349
更新日期:1993-10-01 00:00:00
abstract::Chronic viral infections are often characterized by CD8 T-cell responses with poor cytokine secretion potential and limited expansion of the CD8 T-cell pool, collectively referred to as CD8 T-cell exhaustion. Exhaustion of lymphocytic choriomeningitis virus (LCMV)-specific CD8 T cells was shown to be partially regulat...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxp107
更新日期:2010-01-01 00:00:00
abstract::Antibody responses to ingested antigens can be inhibited by a mechanism known as oral tolerance which acts to prevent excessive stimulation from luminal contents. Local IgA responses can be induced in this non-responsive environment and during intestinal inflammation, mucosal IgG responses can also be increased. The p...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/4.9.975
更新日期:1992-09-01 00:00:00
abstract::A small proportion of the sIg+ B lymphocytes in peripheral lymphoid organs [22% in spleen and 6% in lymph node (LN)] in rat carries the Thy-1 antigen. These Thy-1+ B cells represent newly formed bone marrow (BM) derived (or immature) B cells. In this study we investigated the kinetic behavior of Thy-1+ and Thy-1- B ce...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/5.7.735
更新日期:1993-07-01 00:00:00
abstract::Antibody to phosphatidyl choline (PtC) is produced spontaneously in mice, by approximately 2-10% of naturally occurring CD5+ (B1) B cells in the peritoneum. Much of this antibody is encoded by the VH11 gene associated with a specific V kappa 9 gene. Constraints on the size and structure of the H chain CDR3 have been d...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/5.11.1365
更新日期:1993-11-01 00:00:00
abstract::It has been demonstrated that in vivo T cell priming requires CD154-CD40 interaction, which is suggested to be critical in the induction of co-stimulatory activities on antigen-presenting cells (APC). In the current study, we demonstrate that in vivo administration of a high dose of a superantigen, staphylococcal ente...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxg080
更新日期:2003-07-01 00:00:00
abstract::Sphingosine 1-phosphate (S1P) and S1P receptor 1 (S1P1) play an important role in the egress of mature CD4 or CD8 single-positive (SP) thymocytes from the thymus. Fingolimod hydrochloride (FTY720), an S1P1 functional antagonist, induced significant accumulation of CD62L(high)CD69(low) mature SP thymocytes in the thymi...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxt069
更新日期:2014-05-01 00:00:00
abstract::We have previously shown that the occurrence of CD45RA+ adult mouse thymocytes is strain-dependent, e.g. constituting approximately 0.6% in C57BL/Icrf and approximately 2.5% in BALB/c (Huby, R. and Goff, L., 1992. Eur. J. Immunol. 22:1659). Here we show that irrespective of strain, the thymus contains approximately 0....
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/4.11.1303
更新日期:1992-11-01 00:00:00
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
doi:10.1093/intimm/dxt076
更新日期:2014-06-01 00:00:00
abstract::The adaptive immune response is involved in the development and progression of atherosclerosis and IL-17A(+) cells play a role in this disease. Although elevated number of CD4(+) IL-17A(+) (Th17) and IL-17A(+)TCRγδ(+) T cells are found within murine atherosclerotic aortas and human plaques, the mechanisms governing IL...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxv068
更新日期:2016-05-01 00:00:00
abstract::We have previously shown that the surface alphabeta T cell antigen receptor (TCR).CD3 complex borne by human CD4(+) and CD8(+) T lymphocytes can be distinguished using mAbs. Using two unrelated sets of antibodies, we have now extended this finding to the surface alphabetaTCR.CD3 of seven additional mammalian species (...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxn081
更新日期:2008-10-01 00:00:00
abstract::The class II trans-activator (CIITA) is a bi- or multi-functional domain protein which plays a critical role in the expression of MHC class II genes. We report that removal of the N-terminal 151 amino acids, encompassing all of the acidic domain but leaving intact the proline/serine/threonine-rich domain, results in a...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/9.10.1545
更新日期:1997-10-01 00:00:00
abstract::To investigate the involvement of retinoic acid receptor (RAR)-alpha in allograft rejection, we investigated the effect of a novel selective agonist to the receptor, ER-38925, in a mouse cardiac allograft model. Prophylactic treatment with ER-38925 inhibited the acute rejection of the mouse cardiac allograft (BALB/c -...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh066
更新日期:2004-05-01 00:00:00