Abstract:
:The early-life immune environment has been implicated as a modulator of acute lymphoblastic leukemia (ALL) development in children, with infection being associated with significant changes in ALL risk. Furthermore, polymorphisms in several cytokine genes, including IL-10 and IFN-γ, are associated with leukemia development. However, the mechanisms and timing of these influences remain unknown. Here, we use the Eμ-ret transgenic mouse model of B-cell precursor ALL to assess the influence of IFN-γ on the early-life burden of leukemia-initiating cells. The absence of IFN-γ activity resulted in greater numbers of leukemia-initiating cells early in life and was associated with accelerated leukemia onset. The leukemia-initiating cells from IFN-γ-knockout mice had reduced suppressor of cytokine signaling (SOCS-1) expression, were significantly more sensitive to IFN-γ, and exhibited more rapid expansion in vivo than their wild-type counterparts. However, sensitivity to this inhibitory pathway was lost in fully transformed IFN-γ-knockout leukemia cells. These results demonstrate that the influence of IFN-γ on ALL progression may not be mediated by selection of nascent transformed cells but rather through a general SOCS-mediated reduction in B-cell precursor proliferation. Thus, while cytokine levels may influence leukemia at multiple points during disease progression, our study indicates a significant early influence of basal, infection-independent cytokine production on leukemogenesis.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Fidanza M,Seif AE,Jo S,Kariminia A,Rolf N,Sly LM,Grupp SA,Reid GSDdoi
10.1002/eji.201646806subject
Has Abstractpub_date
2017-05-01 00:00:00pages
892-899issue
5eissn
0014-2980issn
1521-4141journal_volume
47pub_type
杂志文章abstract::One of the clear paradoxes in tumor immunology is the fact that cross-presentation of cell-associated tumor antigens to CD8(+) T cells is efficient, yet CTL generation is weak, and tumors continue to grow. We examined, for the first time whether this may be due to alterations in the phenotype or function of cross-pres...
journal_title:European journal of immunology
pub_type: 杂志文章
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更新日期:2010-06-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830230831
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abstract::In rheumatoid arthritis (RA), T cells in the inflamed joint are considered to play a crucial role in the pathogenesis. However, despite the fact that synovial T cells have an activated memory phenotype, they are functionally suppressed upon combined CD3 and CD28 stimulation. Here, we analyzed the contribution of both ...
journal_title:European journal of immunology
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更新日期:1998-05-01 00:00:00
abstract::The atypical chemokine receptor CXCR7 binds the chemokines CXCL12 and CXCL11. The receptor is widely expressed and was shown to tune CXCR12-induced responses of CXCR4. Here, the function of CXCR7 was examined at late stages of human B-cell maturation, when B cells differentiate into Ab-secreting plasmablasts. We ident...
journal_title:European journal of immunology
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journal_title:European journal of immunology
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更新日期:1993-11-01 00:00:00
abstract::A mouse HER2-derived peptide, HER2p63 (A) (TYLPANASL), can induce K(d)-restricted mouse cytotoxic T lymphocytes (CTL) and also function as a tumor rejection antigen in an in vivo assay. Since the anchor motif of mouse K(d) for peptide binding has much similarity to that of human HLA-A2402, we asked if human HER2p63 (T...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(200011)30:11<3338::AID-IMMU3338>
更新日期:2000-11-01 00:00:00
abstract::Anti-immunoglobulin antibodies (anti-Ig) provoke the rapid breakdown of phosphatidylinositol bisphosphate (PIP2), elevation of cytoplasmic Ca2+ levels ([Ca2+]i) and activation of protein kinase C (PKC) in B lymphocytes. Tumor-promoting phorbol esters, like phorbol myristate acetate, also activate PKC, but inhibit anti...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830170119
更新日期:1987-01-01 00:00:00
abstract::gp140 is the Epstein-Barr virus receptor and the C3d receptor (EBVR/C3dR) of human B lymphocytes. Recently, we have shown that cross-linking of EBVR/C3dR on cell surface by polyclonal anti-gp140 induced B cell activation, in presence of T cell factors. Immunoregulatory abnormalities of EBV-induced B cell activation ha...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830161108
更新日期:1986-11-01 00:00:00
abstract::Inflammatory bowel disease (IBD) is characterized by a dysregulated intestinal immune response with elevated levels of the Th1 cytokines TNF, IL-12 and IFN-gamma. The luminal flora has been implicated as a major factor contributing to the initiation and perpetuation of chronic intestinal inflammation by as yet unknown...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(200207)32:7<2084::AID-IMMU2084>3
更新日期:2002-07-01 00:00:00
abstract::Interleukin 2 (IL2)-dependent cytolytic hybrids usually loose IL2 dependence and cytolytic activity concomittantly. Here we describe an exceptional IL2-independent variant which lost IL2 receptor but retained cytolytic activity. When the IL2-independent cytolytic hybrid cells were fused with IL2-dependent cytolytic cl...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830150803
更新日期:1985-08-01 00:00:00
abstract::Empty major histocompatibility complex (MHC) class I molecules present on the surface of RMA-S (26 degrees C) cells were loaded with the iodinated peptides APGNYPAL, FAPGNYPAL (SEV-9) and RGYVYQGL (VSV-8), respectively. The thermostability of these peptide-loaded MHC class I molecules was assessed using temperature gr...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830230847
更新日期:1993-08-01 00:00:00
abstract::Interleukin-HP1 (HP1) is a murine T cell-derived lymphokine, originally described as a growth factor for B cell hybridomas and plasmacytomas, that was recently shown to stimulate growth and differentiation of normal B and T lymphocytes. Here, we describe a cDNA for HP1 that was isolated from a library prepared using m...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830180202
更新日期:1988-02-01 00:00:00
abstract::The monoclonal antibody W6/32.1 recognizes a public determinant on the HLA-A, B and C antigens of all tested human haplotypes. Though the antibody does not bind to normal mouse cells of any H-2 haplotype, it does show an unexpected specificity for the T cell leukemia line MBL-2 from a C57BL/6 mouse. It is shown that t...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830130213
更新日期:1983-02-01 00:00:00
abstract::Antimicrobial peptides human beta-defensins (hBD) are mainly produced by epithelia of several organs including skin, and participate in innate immunity by killing invading pathogens. Besides their microbicidal activities, hBD activate several inflammatory and immune cells. Since hBD are generated by tissues where mast...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200636379
更新日期:2007-02-01 00:00:00
abstract::Polymorphonuclear neutrophils (PMN) modulate the adaptive immune response through interactions with immature dendritic cells (iDC) while spontaneous apoptotic neutrophils PMNapo (PMNapo) may have an inhibitory effect on DC functions. We investigate the effect exerted by PMNapo in DC maturation and the role of Mycobact...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200636771
更新日期:2007-06-01 00:00:00
abstract::A majority of immunodominant epitopes of mycobacterial antigens are known to be recognized by murine T cells in the context of several H-2 haplotypes. In this study, we established the frequency of T cells able to recognize these peptides promiscuously, i.e. in the context of allogeneic antigen-presenting cells, using...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830251009
更新日期:1995-10-01 00:00:00
abstract::DC not only activate CD4 T (Th) cell and cytotoxic CD8 T cell (CTL) responses against pathogens, but they also tolerize autoreactive T cells in order to avoid autoimmunity. Previous studies have demonstrated that steady-state DC can tolerize naïve CTL, naïve Th cells and memory CTL. A study in this issue of the Europe...
journal_title:European journal of immunology
pub_type:
doi:10.1002/eji.201040704
更新日期:2010-07-01 00:00:00
abstract::A previously designed isotopic in vivo method for measuring delayed hypersensitivity was used with nonantigenic (or weakly antigenic) phlogogenic substances. A strong reaction was observed in some circumstances, witnessing the fact that the method has a specific and a nonspecific component. The reaction is drastically...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830060606
更新日期:1976-06-01 00:00:00
abstract::Stilbene disulfonates are known to competitively inhibit Cl-/HCO3- flux through Band 3-related anion exchange (AE) proteins. To study the role of AE in lymphocyte activation, stilbene disulfonates were added to cultures of rat splenocytes (SPL). Four different stilbene derivatives were tested and each directly stimula...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830220509
更新日期:1992-05-01 00:00:00
abstract::IL-15 is involved in lymphocyte homeostasis. To investigate the role of IL-15 in the skin in vivo, mice were generated that overexpress IL-15 in keratinocytes, resulting in increased IL-15 protein levels in the skin but not elevated IL-15 serum concentrations. Keratin 14 (K14)-IL-15 transgenic (tg) mice showed increas...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200324785
更新日期:2004-07-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830220724
更新日期:1992-07-01 00:00:00
abstract::Activated human monocytes are a source of numerous beta-chemokines. The present study was conducted to determine whether these cells produce the human beta-chemokine I-309 and to compare the induction requirements of I-309 to those of other beta-chemokines. We demonstrate that appropriately stimulated adherence-purifi...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830270317
更新日期:1997-03-01 00:00:00
abstract::Just over a decade ago, it was established that NK cells in the thymus do not follow precisely the same developmental pathway as conventional NK cells that develop in the bone marrow. Subsequently, it has emerged that NK cells are one branch of a family of innate lymphoid cells (ILCs). ILC1s and thymic NK cells have, ...
journal_title:European journal of immunology
pub_type: 评论,杂志文章
doi:10.1002/eji.201747038
更新日期:2017-05-01 00:00:00
abstract::High frequencies of CD5+TcR alpha/beta- T cells were induced in the peritoneal cavity of rats immunized with syngeneic W439 lymphoma cells. These TcR alpha/beta- cells expressed TcR delta mRNA as analyzed by the polymerase chain reaction technique. The delta + (TcR gamma/delta +) T cells were of the CD2+, CD3+, CD4-, ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830211122
更新日期:1991-11-01 00:00:00
abstract::The interaction of KB-V1, a multidrug resistant (MDR) variant of the KB-3-1 human oral carcinoma, with human complement was investigated. KB-V1 cells were found to be more sensitive than KB-3-1 cells to complement-mediated lysis. Detailed analysis of the capacity of KB cells to activate human complement demonstrated t...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830270913
更新日期:1997-09-01 00:00:00
abstract::In order to characterize the murine anti-human xenogeneic mixed lymphocyte reactions (MLR), we studied T cell proliferative responses against various human lymphoid cells by immunization of mice either with cellular or purified HLA-DR antigens. Data presented here indicated that small amounts of soluble HLA-DR antigen...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830171103
更新日期:1987-11-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/(SICI)1521-4141(199910)29:10<3188::AID-IMM
更新日期:1999-10-01 00:00:00
abstract::The immune system relies on homeostatic mechanisms in order to adapt to the changing requirements encountered during steady-state existence and activation by antigen. For T cells, this involves maintenance of a diverse repertoire of naïve cells, rapid elimination of effector cells after pathogen clearance, and long-te...
journal_title:European journal of immunology
pub_type: 杂志文章,评审
doi:10.1002/eji.200939444
更新日期:2009-08-01 00:00:00
abstract::The functional role of the T8 antigen of human T cells was studied by inhibition with anti-T8 monoclonal antibodies (mAb) of the cytotoxic action of T8+ cytotoxic T lymphocyte clones (CTL). All clones were allospecific and directed against HLA-B7. The ability of seven different anti-T8 mAb to inhibit the cytotoxicity ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830161109
更新日期:1986-11-01 00:00:00
abstract::Cross-linking of surface Ig receptors (sIg) by mitogenic forms of anti-Ig antibodies (e.g. F(ab')2 fragments of rabbit anti-Ig) causes the rapid, and prolonged breakdown of phosphatidylinositol 4,5-bisphosphate. This response involves an unidentified guanine nucleotide regulatory protein (termed Gp), which couples sIg...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830190311
更新日期:1989-03-01 00:00:00