Abstract:
:Despite the capacity for antigen-specific activation and rapid clonal expansion, homeostatic mechanisms ensure that the mature immune system contains a relatively stable number of T cells. In recent years, it has become apparent that this stability is a consequence of apoptotic death of most of the specific T cells generated during an immune response. Clearly this process must be tightly regulated in order to retain sufficient T-cell progeny to mediate an effective response, whilst allowing the rapid deletion of these cells at the end of the response to prevent lymphadenopathy and cross-reactive autoimmunity. In this study, the factors that regulate the sensitivity of T cells to apoptosis were investigated in vitro after the induction of primary T-cell activation within a mixed lymphocyte reaction (MLR). It was found that activated T cells rapidly acquire the expression of both Fas and Fas ligand (FasL) on their surface and contain high levels of the precursor form of the pro-apoptotic enzyme, caspase 8 (FLICE). However, these T cells were resistant for up to 5 days to apoptosis following the stimulation of Fas; a maximal apoptotic response was observed after 7 days. This time point coincided with a marked reduction in expression of the FLICE inhibitory protein (FLIP) and maximal activity of caspase 8. At time points beyond day 7, the number of viable cells in the MLR decreased further despite a reduction in the expression of FasL. However, the expression of interleukin-2 (IL-2) at these late time points was low, resulting in a decrease in expression of the anti-apoptotic protein Bcl-2. This can produce apoptosis by allowing leakage of cytochrome-c from mitochondria resulting in direct activation of the caspase cascade. In this study, it is shown that T cells are resistant to apoptosis for the first 5 days after activation as a consequence of insensitivity of the Fas pathway and the presence of intracellular Bcl-2. After between 5 and 7 days, the cells become sensitive to Fas-mediated apoptosis while retaining Bcl-2 expression. At later time points, Fas ligation is reduced but the cells respond to a decreased availability of IL-2 by reducing Bcl-2 expression; this encourages further apoptosis by allowing the direct activation of caspase enzymes.
journal_name
Immunologyjournal_title
Immunologyauthors
O'Flaherty E,Wong WK,Pettit SJ,Seymour K,Ali S,Kirby JAdoi
10.1046/j.1365-2567.2000.00048.xkeywords:
subject
Has Abstractpub_date
2000-07-01 00:00:00pages
289-99issue
3eissn
0019-2805issn
1365-2567pii
imm048journal_volume
100pub_type
杂志文章相关文献
IMMUNOLOGY文献大全abstract::The interaction of mouse intestinal mast cell proteinase (IMCP) with serine proteinase inhibitors (serpins) in blood was analysed: (i) by examining the capacity of the inhibitors in blood to block the binding of the irreversible serine esterase inhibitor [3H]diisopropyl fluorophosphate (DFP); (ii) by Western blotting....
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1990-01-01 00:00:00
abstract::This study investigates the effect of feeding fermented milks with Lactobacillus casei, Lactobacillus acidophilus and a mixture of both micro-organisms on the specific and non-specific host defence mechanisms in Swiss mice. Animals fed with fermented milk for 8 days (100 micrograms/day) showed an increase in both phag...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract::The effect of long chain and medium chain fatty acid absorption on transport and mitogen-induced blast transformation of lymphocytes in intestinal lymphatics was investigated. Intestinal lymph was collected from mesenteric lymph duct cannulated rats maintained in Bollman's cage. Following the intraduodenal administrat...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract::Peripheral blood lymphocytes from patients with Hashimoto's thyroiditis have been cultured for 2--3 weeks in Marbrook flasks. During this period, readily detectable amounts of thyroglobulin and microsomal antibodies were synthesized by the cells and secreted into the culture medium. Gel filtration studies indicated th...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1979-01-01 00:00:00
abstract::Human blood monocytes were activated by bacterial lipopolysaccharide endotoxin (LPS) (10 ng/ml) for cytotoxicity of WEHI-164 mouse fibrosarcoma cells, determined by release of 51Cr from WEHI-164 tumour cells incubated with monocyte supernatants. The chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (FMLP) aug...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1992-05-01 00:00:00
abstract::Natural infection by mouse hepatitis virus (MHV) can affect interpretation of immunological studies in mice. MHV, a collective term describing a group of corona viruses, is found in natural infections in over 70% of laboratory mouse populations in the U.S.A. and Canada. Natural outbreaks of MHV in our animal colony af...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1992-03-01 00:00:00
abstract::Thymocytes expressing self-reactive T-cell receptors (TCR) are eliminated in the thymus through a TCR-mediated signal. This cell death signal (negative selection) generates nuclear morphological change and DNA fragmentation in thymocytes. However, the pathway leading to DNA fragmentation of thymocytes following TCR en...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1046/j.1365-2567.2002.01347.x
更新日期:2002-04-01 00:00:00
abstract::Using cloned human helper T lymphocytes reactive with a 24 amino acid peptide (p20) of the carboxyl terminal of the HA-1 molecule of influenza haemagglutinin we have investigated the influence of antigen structure on the activation and in the induction of antigen specific unresponsiveness of T cells. For this analysis...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1986-03-01 00:00:00
abstract::Undesired immunological responses to products of therapeutic gene replacement have been obstacles to successful gene therapy. Understanding such responses of the host immune system to achieve immunological tolerance to a transferred gene product is therefore crucial. In this article, we review relevant studies of immu...
journal_title:Immunology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2567.2009.03069.x
更新日期:2009-05-01 00:00:00
abstract::Secretory component (SC or polymeric immunoglobulin receptor) on mucosal epithelial cells mediates transcytosis of polymeric immunoglobulin into external fluids and functions as a receptor for polymeric immunoglobulin. SC expression in a human colonic adenocarcinoma cell line, HT-29 has been reported to be up-regulate...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1046/j.1365-2567.1997.00341.x
更新日期:1997-10-01 00:00:00
abstract::The isolation and characterization of a new eosinophil-derived protein, eosinophil protein X (EPX) is here described. The purified EPX is a highly basic glycoprotein and shows one band on sodium dodecyl sulphate polyacrylamide gel electrophoresis and on agarose electrophoresis. The molecular weight of the unreduced pr...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1983-09-01 00:00:00
abstract::Interleukin-1 (IL-1) is an important mediator of inflammation and has been implicated in several forms of immunopathology. Here we have investigated whether IL-1 plays a role in the enteropathy which occurs during a graft-versus-host reaction (GVHR) in mice. Non-irradiated (CBA x BALB/c) F1 mice with GVHR had increase...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1993-09-01 00:00:00
abstract::A soluble form of Fc epsilon RII/CD23 is spontaneously released from most lymphoblastoid cell lines established by the Epstein-Barr virus (EBV). Such a product was purified on an IgE-Sepharose column and its pyrogenic effect was investigated in rabbits. This preparation induced a monophasic fever in rabbits, with a pe...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1991-08-01 00:00:00
abstract::Studies in long-term non-progressors (LTNP) have suggested that the quality of the CD8(+) response may involve protective human leucocyte antigen (HLA) class I alleles. However, studies examining the expansion ability of different functional CD8(+) T cells and their association with HLA class I alleles are lacking. LT...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2567.2011.03490.x
更新日期:2011-11-01 00:00:00
abstract::Human leukaemia and lymphoma cell lines were investigated as stimulating cells in an allogeneic mixed lymphocyte response. Purified T cells and unfractionated mononuclear cells from normal donors were used as responders. The cell lines fell into three groups: (i) those which stimulated allogeneic responder T cells in ...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1982-12-01 00:00:00
abstract::Silica, or silicon dioxide, has been shown to be toxic for macrophages. This is probably because it damages phagolysosomal membranes, allowing lysosomal enzymes to disrupt the cell. Neutrophils also take up particles such as silica and in addition they contain lysosomes. The purpose of this study was to determine whet...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1986-12-01 00:00:00
abstract::In order to study the precise localization pattern of anti-TNP antibody-forming cells (AFCs) during the early primary immune response against TNP conjugated TD (thymus-dependent) and TI-2 (thymus-independent type-2) antigens, rats received an intravenous injection with either TNP-keyhole limpet haemocyanin (KLH) or wi...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1986-03-01 00:00:00
abstract::Doxorubicin-stimulated whole rat glomeruli and dissociated mesangial and resident glomerular macrophage cells produced the release of interleukin (IL)-1 beta cytokine. This activity increased after the addition of lipopolysaccharide (LPS) or LPS plus indomethacin to the cultures. In the presence of WEB2086 [platelet-a...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract::From our experiments and those of others in which cells were cultured at a density of 100,000 cells per well, it has been suggested that autoantibody production against mouse bromelain-treated erythrocytes (mouse brom-RBC) was independent of T cells, and further, was enhanced by the removal of T cells from responsive ...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1987-06-01 00:00:00
abstract::Veiled cells (VC), isolated from the thoracic duct of irradiated lymphadenectomized mice (MLNX) or peritoneal macrophages (PM phi were incubated with isotope-labelled hen egg lysozyme (HEL), purified protein derivative (PPD) or keyhole limpet haemocyanin (KLH) in vitro. About 2-10 times less antigen was associated wit...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1989-11-01 00:00:00
abstract::Epididymitis represents a serious threat to male fertility and usually develops following secondary bacterial infection of the epididymis such as urinary tract infections or sexually transmitted diseases. Surprisingly, very little is known about the innate host response triggered by bacterial infection in the male rep...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2567.2007.02763.x
更新日期:2008-06-01 00:00:00
abstract::It is now well accepted that sex hormones have immunoregulatory activity and may prevent exacerbations in multiple sclerosis during pregnancy. Our previous studies demonstrated that oestrogen (17β-oestradiol; E(2) ) protection against experimental autoimmune encephalomyelitis (EAE) is mediated mainly through oestrogen...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/imm.12013
更新日期:2012-12-01 00:00:00
abstract::Male and female spleen cells were compared before and after culture for their cytotoxicity to autologous-embryo fibroblasts. Cultures of male cells developed significantly greater reactivity than cultures of female cells. Moreover, while the cytotoxicity derived from cultures of male cells was totally abolished by tre...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1976-10-01 00:00:00
abstract::Signal transducers and activators of transcription (STATs) are key molecular determinants of T-cell fate and effector function. Several inflammatory diseases are characterized by an altered balance of T-cell phenotypes and cytokine secretion. STATs, therefore, represent viable therapeutic targets in numerous pathologi...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/imm.12851
更新日期:2018-04-01 00:00:00
abstract::Immunoglobulin E (IgE)-dependent mechanisms play a pivotal role in mediating allergic disease. Previously, VH-Cepsilon transcripts from blood or spleen of atopic asthmatics have been analysed for VH gene usage and patterns of somatic mutation. An over-representation of the minor VH5 family has been observed, consisten...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1046/j.1365-2567.1999.00910.x
更新日期:1999-12-01 00:00:00
abstract::A neutral protease with a molecular weight of about 14,00 was separated at acid pH from rabbit neutrophils and then partially purified by elution on DEAE-Sephadex, CM-Sephadex and Sephadex G-75 in that order. This enzyme was inactivated by diisopropyl fluorophosphate (DFP), phenylmethyl sulphonylfluoride (PMSF), soybe...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1978-07-01 00:00:00
abstract::The functional avidity of a cytotoxic T lymphocyte (CTL) is known to be a critical determinant of the efficacy with which it clears pathogens. High avidity cells, which are by definition highly sensitive to peptide antigen, are superior for elimination of viruses and tumours. Our studies have established the ability o...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2567.2011.03440.x
更新日期:2011-07-01 00:00:00
abstract::B-lymphocyte maturation is considered to be independent of the thymus. However, there is circumstantial evidence suggesting that it may be impaired in nude animals that lack the thymus. Our study shows that the proportion of immature B-lymphocyte subsets (CD90(high) IgM(high) and CD90(high) IgM(low)) was significantly...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2567.2005.02226.x
更新日期:2005-11-01 00:00:00
abstract::The suppression of immune responsiveness to heterologous antigenic stimulation during concurrent infection with Nematospiroides dubius was reproduced using soluble antigens derived from adult parasites. Immunosuppression appeared to be selective in that the administration of equivalent quantities of an irrelevant hete...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1984-04-01 00:00:00
abstract::The primary immunoglobulin repertoire of chickens is generated not by gene rearrangement but by a subsequent process of gene conversion in proliferating immature B cells within the follicles of a specialized gut-associated lymphoid organ, the bursa of Fabricius. Neonatal infection with infectious bursal disease virus ...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2567.2006.02332.x
更新日期:2006-04-01 00:00:00