Biomedical subjects

B Mari

Publications and source records attributed to B Mari.

At least 19 recordsLinked to original sources

PubMed2006

A survey of the signaling pathways involved in megakaryocytic differentiation of the human K562 leukemia cell line by molecular and c-DNA array analysis.

The K562 cell line serves as a model to study the molecular mechanisms associated with leukemia differentiation. We show here that cotreatment of K562 cells with PMA and low doses of SB202190 (SB), an inhibitor of the p38 MAPK pathway, induced a majority of cells to differentiate towards the megakaryocytic lineage. Electronic microscopy analysis showed that K562 cells treated with PMA+SB exhibited characteristic features of physiological megakaryocytic differentiation including the presence of vacuoles and demarcation membranes. Differentiation was also accompanied by a net increase in megakaryocytic markers and a reduction of erythroid markers, especially when both effectors were present. PMA effect was selectively mediated by new PKC isoforms. Differentiation of K562 cells by the combination of PMA and SB required Erk1/2 activation, a threshold of JNK activation and p38 MAPK inhibition. Interestingly, higher concentrations of SB, which drastically activated JNK, blocked megakaryocytic differentiation, and considerably increased cell death in the presence of PMA. c-DNA microarray membranes and PCR analysis allow us to identify a set of genes modulated during PMA-induced K562 cell differentiation. Several gene families identified in our screening, including ephrins receptors and some angiogenic factors, had never been reported so far to be regulated during megakaryocytic differentiation.

Base Sequence↗

PubMed2002

T and B leukemic cell lines exhibit different requirements for cell death: correlation between caspase activation, DFF40/DFF45 expression, DNA fragmentation and apoptosis in T cell lines but not in Burkitt's lymphoma.

The execution phase of apoptosis occurs through the activation and function of caspases which cleave key substrates that orchestrate the death process. Here, we have compared the sensitivity of various T and B cell lines to death receptor or staurosporine-induced apoptosis. First, we found a lack of correlation between death receptor expression and sensitivity to Fas or Trail. By contrast, a correlation between caspase activation, DNA fragmentation and cell death in T cell lines was evidenced. Among T cells, CEM underwent apoptosis in response to CH11 but were resistant to Trail in agreement with the absence of Trail receptors (DR4 and DR5) on their surface. The B cell line SKW 6.4 was sensitive to CH11 and staurosporine but resistant to Trail. As B cell lines expressed significant levels of DR4 and DR5, resistance to Trail in SKW 6.4 is likely due to the expression of the decoy receptor DcR1. Burkitt's lymphoma such as RPMI 8866 and Raji did not exhibit DNA fragmentation in response to CH11, Trail or staurosporine but showed long-term caspase-dependent loss of viability upon effector treatment. The B cell lines used in this study express very weak or undetectable levels of DFF40 and relatively high levels of DFF45. Interestingly, cytosolic extracts from RPMI 88.66 but not other B lymphoma exhibit altered levels of cytochrome c-dependent caspase activation. Taken together, our results show that: (1) death receptor expression does not correlate with sensitivity to apoptosis; (2) the very low ratio of DFF40 vs. DFF45 is unlikely to explain by itself the lack of DNA fragmentation observed in certain B cell lines; and (3) a defective cytochrome c-dependent caspase activation might account at least in part for the insensitivity of certain Burkitt's lymphoma (RPMI 88.66) to apoptosis. Thus it seems that resistance of Burkitt's lymphoma to apoptosis is not governed by a general mechanism, but is rather multifactorial and differs from one cell line to another.

Antineoplastic Agents↗

PubMed2001

Establishment of two new human bladder carcinoma cell lines, CAL 29 and CAL 185. Comparative study of cell scattering and epithelial to mesenchyme transition induced by growth factors.

We describe here two new human urothelial carcinoma cell lines, CAL 29 and CAL 185, established from two patients with high-grade tumours and which display very different properties in vitro. We have shown that CAL 29 cells were tumorigenic in mice and expressed characteristic features of both cell scattering and transition from epithelial to mesenchymal phenotype (EMT) after triggering by the EGF receptor ligands, TGFalpha and EGF. At the opposite, the CAL 185 cells were not tumorigenic in mice and neither scattered nor expressed vimentin intermediary filaments in the presence of growth factors. We further demonstrated that CAL 29 cell scattering was reversible after growth factor removal and that both scattering and EMT were markedly impaired after treatment with MEK, Src and PI3-kinase inhibitors suggesting that these kinases might be important components of the cellular responses to EGF and TGF-alpha leading to scattering and EMT. These agents could help to understand the intracellular pathways involved in invasiveness and to find new targets for limiting metastasis. In conclusion, these two new cell lines could be good models to dissect the molecular mechanisms involved in invasion and metastasis development in human bladder cancer.

Aged↗

PubMed2001

Differential requirements for ERK1/2 and P38 MAPK activation by thrombin in T cells. Role of P59Fyn and PKCepsilon.

Activation of the mitogen-activated protein kinase (MAPK) cascade is a well documented mechanism for the G-protein-coupled receptors. Here, we have analysed the requirements for ERKs and p38 MAPK activation by thrombin in Jurkat T cells. We show that thrombin-mediated ERKs activation requires both PTK and PKC activities, whereas p38 MAPK activation is dependent only on PTKs. Thrombin-induced ERK and p38 MAPK activation was more pronounced in p56Lck deficient cells indicating that this PTK exerts a negative control on MAPK activity. Accordingly, overexpression of p50 Csk a kinase that inactivates p56Lck induced constitutive activation of ERKs. Requirement for a Src kinase was evidenced by expression of a constitutively active form of p59Fyn in Jurkat cells. Besides its effect on tyrosine phosphorylation events, thrombin also triggered a rapid and robust redistribution of PKCepsilon and delta from the cytosol to the membrane. Expression of constitutively active and dominant negative PKCepsilon demonstrates the pivotal role of this PKC isoform in ERKs activation by thrombin. These data are consistent with a model where thrombin induces ERK activation via both PKC-dependent and independent pathways, whereas p38 MAPK activation requires only PTKs. The PKC-independent pathway requires Src kinases other than p56Lck more likely p59Fyn, while the PKC-dependent mechanism depends on PKCepsilon

Benzoquinones↗

PubMed2001

Pulmonary nocardiosis: clinical experience in ten cases.

BACKGROUND: Pulmonary nocardiosis is an infrequent infection whose incidence seems to be increasing due to a higher degree of clinical suspicion and the increasing number of immunosuppressive factors. OBJECTIVE: To study the predisposing factors, clinical characteristics, diagnostic procedures, treatment and progress of pulmonary nocardiosis (PN). METHODS: Review of 10 patients (9 male, 1 female, mean age 61) with PN in a 600-bed teaching hospital, diagnosed from 1992 to 1999. RESULTS: Associated diseases observed were chronic obstructive pulmonary disease (COPD) in 6 patients, human immunodeficiency virus (HIV) infection in 3 and polymyalgia rheumatica in 1. Four patients had received oral corticotherapy for COPD for over a year (mean dose 13 mg/day of prednisone or equivalent). The main reason for consultation was an increase in dyspnea in the patients with COPD (6/6) and fever in those with HIV (3/3). Mean time between onset of symptoms and diagnosis was 5 weeks. In 8 patients, the infection occurred outside the hospital setting. The infection was restricted to the lung in 9/10; in the remaining case, the central nervous system (CNS) and subcutaneous tissue were affected. Lobar or multilobar consolidation was the most frequent radiographic pattern found (6/10). Sputum culture was positive when performed (8 cases). Diagnosis was made or confirmed by bronchoscopy (bronchoaspirate or protected specimen brush) in 5 patients. Germs isolated were: Nocardia asteroides (8/10), Nocardia farcinica (1/10), Nocardia otitidiscaviarum (1/10). Cotrimoxazole was the most used empirical treatment (6/10). Resolution was achieved in 5 cases. Four subjects died: 1 HIV patient with disseminated nocardiosis, and 3 COPD patients, 2 of whom had received long-term corticotherapy. Illness recurred in only 1 case, due to failure to comply with treatment. CONCLUSIONS: (1) In our geographical setting Nocardia presents as a subacute or chronic pulmonary infection, mainly outside the hospital. (2) It tends to affect only the lung. (3) Diagnosis requires a high clinical suspicion, and can be made on the basis of a sputum culture. (4) Nocardia tends to attack patients with underlying COPD, or immunodepressed patients treated with glucocorticoids, or patients with HIV infection. (5) Mortality is high in both COPD and HIV patients. (6) In our area, cotrimoxazole seems to be the most commonly prescribed treatment.

Adult↗

PubMed2001

A Jurkat T cell variant resistant to death receptor-induced apoptosis. Correlation with heat shock protein (Hsp) 27 and 70 levels.

Ligation of Fas induces an apoptotic program in Jurkat cells (Jd). We describe a Jurkat T cell variant (Jr) which shows total resistance to Fas-mediated apoptosis but which exhibits sensitivity to non-death-receptor pro-apoptotic stimuli such as staurosporine. Resistance to Fas-induced apoptosis in Jr cells is correlated with high expression of Hsps. A prior heat-shock increases Hsp27 and 70 expression and protects Jd and Jr cells from Fas- and staurosporine-induced apoptosis. Staurosporine, but not the anti-Fas antibody CH11, abrogates constitutive Hsp70 expression at 37 degrees C and staurosporine also inhibit Hsp27 expression in Jd and Jr cells at 42 degrees C. These data suggest that constitutive expression of Hsp27 inhibits Fas-mediated apoptosis, but only induced expression of Hsp70 can protect T cells from staurosporine-induced apoptosis. Thus, Hsp27 could play a role in the regulation of death receptor-mediated apoptosis, while Hsp70 could regulate mitochondrial-dependent cell death.

Apoptosis↗

PubMed2000

Cleavage of the serum response factor during death receptor-induced apoptosis results in an inhibition of the c-FOS promoter transcriptional activity.

The c-FOS protooncogene is rapidly induced by a wide variety of extracellular stimuli including mitogenic signals. Regulation of c-FOS expression is tightly dependent on the serum response element localized within its promoter. Two transcription factors, the serum response factor (SRF) and the ternary complex factor, bind to the serum response element and play a key role in the regulation of the c-FOS promoter activity. In the present study, we show that two death effectors (CH11 and TRAIL) severely impaired the transcriptional activity of the c-FOS promoter in Jurkat T cells. This inhibition can be accounted for by the specific cleavage by caspase 3 of the SRF both in vitro and in vivo, since acetyl-DEVD-aldehyde prevented SRF cleavage and abolished the inhibitory effect of CH11 and TRAIL on the c-FOS promoter activity. Moreover, phorbol myristate acetate, a potent anti-apoptotic effector, was found to protect SRF completely from cleavage by caspase 3 and also to prevent the inhibition of the c-FOS promoter activity by death effectors. Survival factors play an essential function in the regulation of cell growth mainly by regulating the expression of immediate early gene such as c-FOS. In this line, cleavage of SRF at the onset of apoptosis could abrogate the ability of the cell to induce inappropriate survival pathways. All together, our results are consistent with a role of SRF at the interface between cell survival and death pathways.

Apoptosis↗

PubMed2000

Prostaglandin B(2) delivers a co-stimulatory signal leading to T cell activation.

Most of the data accumulated to date on the immunoregulatory effects of prostaglandins (PG) on T cell activation stem from the archetypal inhibitory effect of PGE(2). In this study we provide instead, the first evidence that exogenous PGB(2), a catabolic metabolite of PGE(2), synergizes with signals delivered by T cell receptor (TCR) engagement to induce interleukin-2 (IL-2) production and IL-2 receptor (IL-2R) alpha-expression in Jurkat cells. Accordingly, PGB(2) enhances the proliferation of anti-CD3-activated peripheral blood lymphocytes (PBL). In terms of cellular signaling, we present evidence that PGB(2) activates tyrosine kinase activities and efficiently increases c-fos mRNA expression and nuclear factor-kappa B (NF-kappa B) translocation to the nucleus. Owing to these features, PGB(2) appears as a new lipid mediator capable of delivering an ancillary signal leading to T lymphocyte activation.

Antigens, CD↗

PubMed1999

Cleavage and relocation of the tyrosine kinase P59FYN during Fas-mediated apoptosis in T lymphocytes.

Ligation of Fas with its natural ligand or with anti-Fas antibodies induces an apoptotic program in Fas sensitive cells. We report here the identification of the tyrosine kinase p59Fyn as a substrate for CPP32-like proteinases and more particularly caspase 3 during Fas-mediated apoptosis in Jurkat T cells. Inhibition of CPP32-like proteinases by Ac-Asp-Glu-Val-Asp-aldehyde but not by Ac-Tyr-Val-Ala-Asp-aldehyde prevents CPP32, PARP and p59Fyn cleavage indicating that CPP32 or CPP32-like proteinases are responsible for the cleavage of p59Fyn. Cleavage occurs in the N-terminal domain of p59Fyn between Asp19 and Gly20 and is accompanied by relocation of an active p57Fyn kinase to cytoplasm of Fas-stimulated Jurkat cells as judged by both biochemical and confocal microscopy experiments. Thus, p59Fyn relocation and activity may play an important role during Fas-mediated cell death in human T lymphocytes.

Apoptosis↗

PubMed1998

[Examination of the sentinel lymph node in malignant melanoma].

The authors report about a new "lymphatic-mapping" method (by means of patent blue staining) by which it is able to detect regional (sentinel) lymph node, into which the first metastasis is occurred. Experiences were made known with 15 patients. The by "lymphatic mapping" detected and removed sentinel lymph node has an, important role not only in determination of staging, but also in indication of prophylactic block-dissection, too.

Humans↗

PubMed1998

Differential expression of the Kell blood group and CD10 antigens: two related membrane metallopeptidases during differentiation of K562 cells by phorbol ester and hemin.

The erythroleukemic cell line K562 can undergo further differentiation in erythroid or megakaryocytic lineage depending on the nature of the stimulus. Phorbol ester (PMA) stimulates megakaryocytic development whereas hemin promotes erythroid differentiation of these cells. We have examined the effect of PMA and hemin on the expression of the Kell blood group and CD10 antigens, two related proteins that belong to a family of membrane-bound neutral metalloendopeptidases. We show here that differentiation of K562 cells by PMA in the megakaryocytic lineage results in abolishment of Kell mRNA accumulation and protein expression and, in parallel, the induction of CD10 mRNA accumulation, protein expression, and enzymatic activity. Conversely, differentiation of these cells by hemin in the erythroid lineage is accompanied by an up-regulation of Kell mRNA and protein expression, with no changes in CD10 mRNA and protein expression. Thus, CD10 and Kell can be regarded as specific markers of the differentiation of K562 cells in the megakaryocytic and erythroid lineages, respectively.

Antigens, CD↗

PubMed1997

The type 2 CD10/neutral endopeptidase 24.11 promoter: functional characterization and tissue-specific regulation by CBF/NF-Y isoforms.

The cell surface zinc metalloproteinase CD10/neutral endopeptidase 24.11 ([NEP] neprilysin) functions as part of a regulatory loop to control local concentrations of peptide substrates and associated peptide-mediated signal transduction. The physiologic role of the enzyme depends on available substrates in specific organs and cell types. Although CD10/NEP is expressed on a restricted subset of normal and malignant lymphoid progenitors, the enzyme is also expressed by a variety of epithelial cells. To explore the mechanism of tissue-specific expression of this regulatory enzyme, we characterized the major (type 2) CD10/NEP promoter and identified three functionally active transcription factor binding sites (regions I to III). CBF/NF-Y binds to the inverted CCAAT box in region I, whereas a second positive and a third negative factor bind to regions II and III, respectively. Although region I is required for maximal CD10/NEP-driven luciferase activity in the examined epithelial cell lines, this region is not required for maximal activity in the evaluated lymphoid cell lines. The apparent tissue-specific differences in requirements for region I (and CBF/NF-Y) are of particular interest because lymphoid and epithelial cells express alternatively spliced versions of CBF/NF-Y that differ in biologic activity.

Base Sequence↗

PubMed1997

CD10 (endopeptidase 24.11) is a thymic peptide-degrading enzyme possibly involved in the regulation of thymocyte functions.

Human immature thymocytes express significant levels of the CD10 (endopeptidase 24.11) cell surface antigen. We report here that IOB5, an anti-CD10 mAb, as well as the phorbol ester PMA down-regulate CD10 activity at the surface of human thymocytes. The kinetics of CD10 modulation were drastically different for both effectors, indicating different regulatory mechanisms. We also demonstrated that intact human thymocytes hydrolyze thymopentin and that CD10 significantly participates in this process. Finally, we found that thymopentin and to a lesser extent phosphoramidon, a specific endopeptidase 24.11 inhibitor, induced up-regulation of CD4 and CD8 molecules at the thymocyte cell surface. In view of these results, we suggest that down-regulation of endopeptidase 24.11 at the thymocyte cell surface might reduce its activity toward thymic factors possibly involved in the regulation of thymocyte functions.

Antibodies, Monoclonal↗

PubMed1997

Endopeptidase 24.11 (CD10/NEP) is required for phorbol ester-induced growth arrest in Jurkat T cells.

Jurkat T cells express a functional endopeptidase 24.11 that is involved in the regulation of T cell activation. We have analyzed the effect of ectopic CD10 expression in mutant Jurkat cell clones that fail to express CD10 and, unlike wild-type cells, are resistant to the growth-inhibitory effects of the protein kinase C activator, PMA. No differences in the expression of the mRNA encoding the alpha, beta, gamma, delta, epsilon, and zeta isoforms of PKC were found in parental vs. PMA-resistant Jurkat cells, ruling out the possibility that the defect could be accounted for by an altered expression of one of these isoforms. Phorbol ester-induced growth arrest was not due to apoptosis since PMA failed to trigger DNA fragmentation in parental and mutant Jurkat T cells. CD10 mRNA expression and activity were abrogated in four independent PMA-resistant Jurkat T cell clones compared to parental cells, whereas the activities of several other peptidases were unaffected. Transfection of one mutant clone with a functional endopeptidase 24.11 restored in a significant manner PMA-induced growth arrest in all the clones selected and tested, whereas transfection of an inactive form of endopeptidase 24.11 had no effect, demonstrating that the enzymatic activity of CD10 is critical in the mediation of the PMA growth arrest. The data presented here demonstrate that a functional CD10 is required for PMA-induced growth arrest in Jurkat cells and provide further evidence for a role of endopeptidase 24.11 in the regulation of tumor cell proliferation.

Apoptosis↗

PubMed1997

CD10 is expressed on human thymic epithelial cell lines and modulates thymopentin-induced cell proliferation.

Thymic hormones such as thymopoietin (TP) have been shown to regulate thymocyte differentiation and lymphocyte activation. However, it is not known whether thymopoietin affects thymic epithelial cell (TEC) functions. In this study we have examined the effect of a five amino acid active peptide (TP5), corresponding to amino acids 32-36 of TP, on the proliferation of nontransformed clones of human TEC. Our results indicate that TP5 induced reinitiation of DNA synthesis and potentiated fetal calf serum (FCS)-induced cell growth in postnatal and fetal-derived human TEC. We also found that TEC lines express high levels of endopeptidase 24.11, a cell-surface metallopeptidase also known as the CD10 antigen. We show that TP5 is cleaved by CD10 at the surface of TEC lines, indicating that this endopeptidase may regulate TP5-induced TEC proliferation. Phosphoramidon, a specific endopeptidase 24.11 inhibitor, consistently acts in synergy with TP5 to enhance FCS-induced TEC growth. Hence, we conclude that 1) TP5 alone or in combination with FCS supports the growth of TEC lines, and 2) TEC lines express high levels of CD10, which regulates TP5-induced TEC proliferation by acting as a thymic peptide degrading enzyme.

Antigens, CD↗

PubMed1997

CD10 plays a specific role in early thymic development.

Development of T lymphocyte is a complex process that depends on both thymocytestromal cell interactions and the production of soluble factors such as cytokines, peptides, and hormones. In many tissues, the concentration of active biological peptides is regulated locally by a specialized family of enzymes: the ectopeptidases. We show here that treatment of fetal thymic organ cultures (FTOC) with the specific CD10 (endopeptidase 24.11) inhibitors SCH 32615: (N-[L-(1-carboxy-2-phenyl)ethyl]-L-phenylalanyl-beta-alanine), RB25: (N-(3-[(hydroaxyamino)carbonyl]-2-benzylidene-1-oxopropyl]-N-glyci ne), and thymopentin (TP5) results in the inhibition of thymocyte differentiation. Each agent induces a significant decrease in the number of double positive (CD4+CD8+) cells in favor of the TN (TcR alpha beta-CD4-CD8-) population. RB25 also blocks T lymphocyte differentiation in FTOC when preinjected into pregnant mice. Finally, RB25 and TP5 were also shown to reduce the number of CD44+CD25- and CD44-CD25- thymocytes both in vitro and after preinjection in vivo in day 2 FTOC. Thus, agents that affect endopeptidase 24.11 activity impair T cell development both in vitro and in vivo. Our results show that the CD10 molecule plays a specific role in promoting early T cell development.

Animals↗

PubMed1996

Thrombin and trypsin-induced Ca(2+) mobilization in human T cell lines through interaction with different protease-activated receptors.

This study was conducted to determine whether serine proteinases may induce [Ca(2+)]i mobilization in different hematopoietic cell lines and to analyze their mechanisms of action. We show that in addition to thrombin and thrombin receptor agonist peptide (TRP, SFLLRN), trypsin induced [Ca(2+)]i mobilization in a highly thrombin-sensitive Jurkat T cell clone. Thrombin, TRP, and trypsin were found to induce [Ca(2+)]i release in three different Jurkat T cell clones differing in the level of T cell receptor expression. Similar results were obtained with a prothymocytic leukemic cell line, HPB.ALL, although these cells were much more responsive to trypsin than to thrombin and TRP. Other cell types such as THP1, a myelomonocytic cell line, or CEM, a CD4(+) positive leukemic cell line, were unresponsive to thrombin, TRP, and trypsin. The effect of trypsin was mimicked by SLIGRL, a peptide corresponding to the cleaved amino-terminal sequence of the recently characterized murine trypsin-activated receptor (PAR2). At suboptimal concentrations, the effects of SFLLRN and SLIGRL were additive, whereas saturating doses of peptides did not further increase [Ca(2+)]i mobilization in Jurkat T cells, indicating that both peptides were able to mobilize the same pool of calcium. Northern blot analysis of mRNAs from different leukemic cell lines indicated a remarkable correlation between PAR2 expression in different cell lines and SLIGRL or trypsin responses in the same cells. The expression of the "trypsin receptor" was also confirmed by polymerase chain reaction analysis. Moreover, a 24 h treatment of Jurkat cells by an anti-CD3 monoclonal antibody, a condition known to down-regulate thrombin receptor expression, induced loss of thrombin and TRP responses but only partially affected trypsin stimulation of [Ca(2+)]i release. Finally, after a first stimulation with either thrombin or trypsin, Jurkat cells were still able to respond to trypsin or thrombin, respectively, demonstrating that thrombin and trypsin essentially activated their own receptors. Our data provided evidence that 1) the human T leukemic cell line Jurkat and other T cell lines express at least two different functional protease-activated receptors, the thrombin receptor and a highly sensitive trypsin receptor, likely the human counterpart of the murine PAR2, and 2) at variance with the commonly accepted model, trypsin exerts most of its effect in T leukemic cell lines by thrombin receptor-independent mechanisms.

Animals↗

PubMed1995

The glycosylphosphatidylinositol-anchored CD59 protein stimulates both T cell receptor zeta/ZAP-70-dependent and -independent signaling pathways in T cells.

The glycosylphosphatidylinositol (GPI)-anchored CD59 protein (human protectin) protects cells against complement-induced lysis, binds to CD2 and also transduces activation signals within T cells. We have further examined the biochemical signals transduced by CD59 and addressed its role in regard to the CD3-mediated signaling cascade. We show here that CD59 cross-linking induces a time-dependent activation of p56lck and of p70zap (ZAP-70) in CD3-positive Jurkat cells, leading to the stimulation of the T cell receptor zeta/ZAP-70 signaling cascade and interleukin-2 (IL-2) synthesis. Cross-linking of CD59 on peripheral T cells and thymocytes induces tyrosine phosphorylations identical to those seen in Jurkat cells and this is followed by lymphokine production and proliferation. In contrast, only activation of CD59-associated p56lck occurs in CD3-negative Jurkat cells, while IL-2 production is impaired, consistent with the lack of ZAP-70 tyrosine phosphorylation observed in these cells. CD59 triggers activation events even in the absence of CD3/T cell receptor expression in Jurkat cells. CD59 cross-linking synergizes with sub-optimal doses of phorbol ester for activation of the protein kinase C and of the p42mapk, as shown by in vitro phosphorylation of histone HIIIS and myelin basic protein, respectively, and leads to CD25 but not CD69 expression. In conclusion, at least two signaling pathways are triggered through CD59, the first one involving ZAP-70 activation and leading to IL-2 secretion and a second pathway observed in the absence of ZAP-70 activation leading to CD25 expression. These two pathways are likely to be involved in the modulation of T cell activation by CD59 protein.

Antigens, CD↗