Biomedical subjects

J Y Bonnefoy

Publications and source records attributed to J Y Bonnefoy.

At least 19 recordsLinked to original sources

PubMed1999

Identification of three alternatively spliced variants of human CD28 mRNA.

CD28, expressed by T cells, plays a central role in providing costimulatory signals to T cells. The cd28 gene is organized into 4 exons. An alternatively spliced CD28 mRNA lacking most of the exon 2 has been previously evidenced. We report here that non stimulated human T cells express three additional alternatively spliced variants of CD28 mRNA (CD28a-c) in. The CD28a variant, expressed at similar levels to that of the full length CD28 mRNA encoding for the membrane form, lacks exon 3. This deletion introduces (i) a frame shift resulting in the addition of two extra amino acids and a premature stop codon and, (ii) induces the loss of the transmembrane region, suggesting that it could encodes for a soluble monomeric molecule which conserves the binding sites of CD28. The CD28b and CD28c variants, expressed at a low level compared with CD28a, are generated by deletion of most of the 3' end of exon 2 plus exon 3 and exon 2 plus exon 3, respectively. Activated T cells express only the membrane CD28 mRNA. These results suggest that resting human T cells may constitutively express both membrane and soluble CD28 which can differentially regulate the outcome of the T cell response.

Alternative Splicing↗

PubMed1999

Absence of lung immunopathology following respiratory syncytial virus (RSV) challenge in mice immunized with a recombinant RSV G protein fragment.

The relative immunopathogenic potential of a recombinant fusion protein incorporating residues 130-230 of respiratory syncytial virus (RSV-A) G protein (BBG2Na), formalin-inactivated RSV-A (FI-RSV), and phosphate-buffered saline (PBS) was investigated in mice after immunization and RSV challenge. FI-RSV priming resulted in massive infiltration of B cells and activated CD4(+) and CD8(+) T lymphocytes in mediastinal lymph nodes (MLN) and lungs, where eosinophilia and elevated IFN-gamma, IL-2, -4, -5, -10, and -13 mRNA transcripts were also detected. PBS-primed mice showed only elevated pulmonary IL-2 and IFN-gamma mRNAs, while an activated CD8(+) T cell peak was detected in MLN and lungs. Cell infiltration also occurred in MLN of BBG2Na-immunized mice. However, there was no evidence of T cell, B cell, or granulocyte infiltration or activation in lungs, while transient transcription of Th1-type cytokine genes was evident. The absence of pulmonary infiltration is unlikely due to insufficient viral antigen. Thus, this recombinant fusion RSV G fragment does not prime for adverse pulmonary immunopathologic responses.

Animals↗

PubMed1999

Human effector memory T cells express CD86: a functional role in naive T cell priming.

The glycoprotein CD86 expressed on APCs provides a costimulatory signal necessary for an efficient activation of naive T cells. In contrast, there is controversy about the condition of expression and the function of CD86 on T cells. In this study, we have analyzed the phenotype and the biological activity of CD86+ T cells generated from human PBMC. Results show that CD86 expression on T cells is induced by long term stimulation via CD3 and IL-2R and is down-regulated as the cells become quiescent. The CD86-expressing cells are memory effector T cells: 1) they express CD45RO and high levels of the activation markers CD25, CD54, and HLA-Dr; 2) they selectively express CD30, CD40-ligand, and CD70; and 3) in response to stimulation, most of them produce IFN-gamma before dying by apoptosis. We then analyzed whether CD86 expressed on T cells is functional. Results show that paraformaldehyde-fixed CD86+ T cells enhance the proliferation and production of IFN-gamma by anti-CD3 mAb-stimulated naive T cells and induce proliferation of resting allogenic T cells. All these effects are prevented by neutralizing anti-CD86 mAbs. In contrast, we report no autocrine effect of CD86 in CD86+ T cell activation. In conclusion, these data show that human memory effector T cells express a functional form of CD86 that can costimulate naive T cell responses.

Antigens, CD↗

PubMed1999

The serum albumin-binding region of streptococcal protein G (BB) potentiates the immunogenicity of the G130-230 RSV-A protein.

BBG2Na is a protein comprising residues 130-230 of the respiratory syncytial virus subgroup A (RSV-A) G protein (G2Na) fused to the albumin-binding domain of streptococcal G protein (BB). BBG2Na was cloned, expressed in Escherichia coli and renaturated. In rodent models, this subunit RSV vaccine adjuvanted in Alhydrogel induced specific antibodies and conferred protection to RSV infection. Comparison of the antibody production in a BALB/c mouse model revealed that BBG2Na induced a stronger and earlier G2Na antibody response than G2Na alone, without altering the IgG subclass distribution. To address the role of the BB part, we explored its carrier properties and showed that it is a Th dependent antigen, generating a more potent G2Na-specific B cell memory response and able to generate Th cells that provide help for G2Na antibody production.

Animals↗

PubMed1999

T lymphocytes induce endothelial cell matrix metalloproteinase expression by a CD40L-dependent mechanism: implications for tubule formation.

Neovascularization frequently accompanies chronic immune responses characterized by T cell infiltration and activation. Angiogenesis requires endothelial cells (ECs) to penetrate extracellular matrix, a process that involves matrix metalloproteinases (MMPs). We report here that activated human T cells mediate contact-dependent expression of MMPs in ECs through CD40/CD40 ligand signaling. Ligation of CD40 on ECs induced de novo expression of gelatinase B (MMP-9), increased interstitial collagenase (MMP-1) and stromelysin (MMP-3), and activated gelatinase A (MMP-2). Recombinant human CD40L induced expression of MMPs by human vascular ECs to a greater extent than did maximally effective concentrations of interleukin-1beta or tumor necrosis factor-alpha. Moreover, activation of human vascular ECs through CD40 induced tube formation in a three-dimensional fibrin matrix gel assay, an effect antagonized by a MMP inhibitor. These results demonstrated that activation of ECs by interaction with T cells induced synthesis and release of MMPs and promoted an angiogenic function of ECs via CD40L-CD40 signaling. As vascular cells at the sites of chronic inflammation, such as atherosclerotic plaques, express CD40 and its ligand, our findings suggest that ligation of CD40 on ECs can mediate aspects of vascular remodeling and neovessel formation during atherogenesis and other chronic immune reactions.

CD40 Antigens↗

PubMed1999

Protective efficacy against respiratory syncytial virus following murine neonatal immunization with BBG2Na vaccine: influence of adjuvants and maternal antibodies.

Alum-adsorbed BBG2Na, a recombinant vaccine derived in part from the respiratory syncytial virus (RSV) subgroup A G protein, induced moderate antibody titers after 1 immunization in 1-week-old mice but conferred complete lung protection upon RSV challenge. The anti-BBG2Na IgG1-IgG2a neonatal isotype profile was suggestive of dominant Th2 responses compared with those in adults. Formulation of BBG2Na with a Th1-driving adjuvant efficiently shifted neonatal responses toward a more balanced and adultlike IgG1-IgG2a profile without compromising its protective efficacy. BBG2Na-induced protective immunity was maintained even after early life immunization in the presence of high titers of maternal antibodies. Under these conditions, the protective efficacy (86%-100%) reflected the high capacity of the nonglycosylated G2Na immunogen to escape inhibition by RSV-A-induced maternal antibodies. Thus, immunization with BBG2Na protected against viral challenge despite neonatal immunologic immaturity and the presence of maternal antibodies, two major obstacles to neonatal RSV vaccine development.

Adjuvants, Immunologic↗

PubMed1999

Identification of multiple protective epitopes (protectopes) in the central conserved domain of a prototype human respiratory syncytial virus G protein.

A recombinant fusion protein (BBG2Na) comprising the central conserved domain of the respiratory syncytial virus subgroup A (RSV-A) (Long) G protein (residues 130 to 230) and an albumin binding domain of streptococcal protein G was shown previously to protect mouse upper (URT) and lower (LRT) respiratory tracts against intranasal RSV challenge (U. F. Power, H. Plotnicky-Gilquin, T. Huss, A. Robert, M. Trudel, S. Stahl, M. Uhlén, T. N. Nguyen, and H. Binz, Virology 230:155-166, 1997). Panels of monoclonal antibodies (MAbs) and synthetic peptides were generated to facilitate dissection of the structural elements of this domain implicated in protective efficacy. All MAbs recognized native RSV-A antigens, and five linear B-cell epitopes were identified; these mapped to residues 152 to 163, 165 to 172, 171 to 187 (two overlapping epitopes), and 196 to 204, thereby covering the highly conserved cysteine noose domain. Antibody passive-transfer and peptide immunization studies revealed that all epitopes were implicated in protection of the LRT, but not likely the URT, against RSV-A challenge. Pepscan analyses of anti-RSV-A and anti-BBG2Na murine polyclonal sera revealed lower-level epitope usage within the central conserved region in the former, suggesting diminished immunogenicity of the implicated epitopes in the context of the whole virus. However, Pepscan analyses of RSV-seropositive human sera revealed that all of the murine B-cell protective epitopes (protectopes) that mapped to the central conserved domain were recognized in man. Should these murine protectopes also be implicated in human LRT protection, their clustering around the highly conserved cysteine noose region will have important implications for the development of RSV vaccines.

Animals↗

PubMed1998

Binding of anti-CD23 monoclonal antibody to the leucine zipper motif of FcepsilonRII/CD23 on B cell membrane promotes its proteolytic cleavage. Evidence for an effect on the oligomer/monomer equilibrium.

In the present study we have compared the binding of two monoclonal antibodies to CD23, EBVCS1 and mAb25, which recognize the stalk and the lectin domain, respectively, on the CD23 molecule. At 4 degreesC, EBVCS1 binds to about 10% of the receptors recognized by mAb25 on the B cell surface. At 37 degreesC, whereas mAb25 reaches its maximal binding within a few seconds, EBVCS1 requires 60 min to bind to the same extent. Stabilization of the oligomeric structure of CD23 with IgE strongly affects in a dose-dependent fashion the number of binding sites seen by EBVCS1 but not the t1/2 to reach them, suggesting that EBVCS1 binds to the coiled coil region through an allosteric mechanism. EBVCS1 rapidly down-modulates the membrane CD23 expression with a coincident increase of CD23-soluble fragments in the culture medium, an effect that is inhibited by IgE. In contrast, mAb25, as well as IgE, protects CD23 from proteolytic cleavage and stimulates its endocytosis. These results suggest that EBVCS1 unravels the coiled coil structure of CD23, rendering it more susceptible to proteolytic attack. This supports the oligomeric model proposed previously (Gould, H., Sutton, B., Edmeades, R., and Beavil, A. (1991) Monogr. Allergy 29, 28-49). The biological significance of these observations is discussed.

Allosteric Regulation↗

PubMed1998

The recombinant Klebsiella pneumoniae outer membrane protein OmpA has carrier properties for conjugated antigenic peptides.

Klebsiella pneumoniae OmpA, the 40-kDa major protein of the outer membrane, was cloned and expressed in Escherichia coli. The recombinant protein was produced intracellularly in E. coli as inclusion bodies. Fusion of a short peptide to the N-terminus of native P40 facilitated high-level expression of the recombinant protein. Purified recombinant P40 was analyzed to verify purity and structural integrity. The molecular mass of purified recombinant P40 determined by electrospray mass spectrometry was 37,061 Da, in agreement with the theoretical mass deduced from the DNA sequence. Specific proliferation of recombinant-P40-primed murine lymph node cells in response to recombinant P40 stimulation in vitro indicated the presence of a T-cell epitope on recombinant P40. The induction of high serum antibody titers to a synthetic peptide derived from the attachment protein G of the respiratory syncytial virus when chemically coupled to recombinant P40 indicated that the protein had potent carrier properties.

Amino Acid Sequence↗

PubMed1998

IgE versus IgG4 production can be differentially regulated by IL-10.

Allergen-specific IgE plays a key role in the physiopathology of allergic disorders. This IgE response is usually accompanied by a production of IgG4. Indirect evidence suggests that IgG4 may not be a sensitizing Ab but, in contrast, could be protective. As such, it may be of potential therapeutic interest to selectively modulate IgE vs IgG4 production. To date, IgE and IgG4 switching seems to be controlled by common mechanisms. We report here that IL-10 has a differential effect on IgE vs IgG4 production by PBMC. IL-10 decreases epsilon transcript expression and IgE production induced by IL-4 when added during the first 3 days of in vitro culture, suggesting that IL-10 decreases IL-4-induced IgE switching. In contrast, if added later on B cells that are already IgE switched, IL-10 potentiates IgE production. Interestingly, whatever the time of addition, IL-10 augments IL-4-induced gamma4 transcript expression and IgG4 production, with a maximal effect when added during the first 3 days. As IL-10 is not a switch factor for IgG4, it is likely that IL-10 enhances IgG4 production by potentiating IL-4-induced IgG4 switching. However, IL-10 may also act by enhancing the growth and/or differentiation of cells that are already IgG4 committed. Finally, CD40 ligation reverses the early down-regulating effect of IL-10 on IgE production. These results are the first evidence of a molecule that differentially regulates IgE vs IgG4 production, thereby suggesting the existence of a pathway(s) selectively controlling their production.

Adjuvants, Immunologic↗

PubMed1998

Interleukin-7 (IL-7) enhances class switching to IgE and IgG4 in the presence of T cells via IL-9 and sCD23.

Interleukin-7 (IL-7) is a B-cell growth factor produced by both bone marrow stroma cells and follicular dendritic cells (FDCs) located in primary lymphoid follicles and germinal centers. In this study, we have evaluated the role of IL-7 on human Ig class switching. IL-7 was added to peripheral blood mononuclear cells (PBMCs) or tonsillar B cells in the absence or presence of IL-4 and/or anti-CD40 monoclonal antibody (MoAb). Alone, IL-7 did not affect Ig production by PBMCs or by anti-CD40 MoAb-stimulated B cells. Rather, IL-7 potentiated IL-4-induced IgE and IgG4 production by PBMCs. In parallel, IgG3 production was also enhanced but to a lesser extent, whereas the production of the other isotypes was unaltered. The activity of IL-2, IL-9, or IL-15, which share usage of the common gamma chain for signaling, was also assessed. IL-9, like IL-7, potentiated mainly IgE and IgG4 production by IL-4-stimulated PBMCs. IL-15, in contrast, was ineffective, whereas IL-2 enhanced the production of all isotypes. More precisely, IL-7 potentiation of IgE and IgG4 production required the presence of T cells and was accompanied by an increase of the expression of two soluble molecules favoring preferentially IgE and IgG4 synthesis: CD23 (sCD23) and IL-9. Moreover, neutralizing anti-CD23 and anti-IL-9 antibodies partly inhibited the increase of IgE synthesis induced by IL-7. Thus, IL-7 produced locally in the germinal centers by FDCs may interact with T cells and potentiate human IgE and IgG4 switching by favoring IL-9 and sCD23 production.

B-Lymphocytes↗

PubMed1998

Alpha-1 antitrypsin up-regulates human B cell differentiation selectively into IgE- and IgG4- secreting cells.

Numerous allergens have proteolytic activities. It has been speculated that this property may contribute to their allergenicity. Therefore, we have evaluated the effect of different physiological protease inhibitors (PI) on the regulation of human IgE synthesis. Unexpectedly, the serine PI, alpha-1 antitrypsin, also called alpha-1 protease inhibitor (alpha1PI), induced a potent and selective dose-dependent increase of IgE and IgG4 production by human tonsillar B cells stimulated with the IgE and IgG4 switch factors, IL-4 and anti-CD40 mAb. The other serine PI tested were inefficient. Furthermore, this effect of alpha1PI was accompanied by an increase in (1) germ-line and mature sigma mRNA transcription, (2) proliferation and (3) membrane CD23 and CD21 expression, while the expression of other molecules involved in the regulation of IgE synthesis was unchanged. Since CD23-CD21 pairing plays a crucial role in the up-regulation of IgE synthesis, we have tested whether blocking this interaction affected alpha1PI-increased IgE production. The neutralizing anti-CD23 mAb, Mab 25, partly reversed the IgE increase caused by alpha1PI. Moreover, alpha1PI potentiation of IgE synthesis was prevented by elastase, a natural substrate of alpha1PI, thereby suggesting that alpha1PI may inhibit endogenous B cell enzyme(s) involved in the down-regulation of IgE synthesis. Alpha1PI also potentiated IgE and IgG4 production by IL-4-stimulated peripheral blood mononuclear cells but was not a switch factor for IgE and IgG4 as it was unable to replace IL-4 or anti-CD40 mAb in inducing IgE and IgG4 production. In conclusion, this study shows that alpha1PI acts as a potent co-stimulus for IgE and IgG4 synthesis and suggests that the equilibrium between protease/ protease inhibitor participates in the control of human IgE and IgG4 synthesis.

Antibodies, Monoclonal↗

PubMed1998

Soluble CD21 induces activation and differentiation of human monocytes through binding to membrane CD23.

Interactions between CD23, the low-affinity receptor for IgE, and CD21, the C3d/EBV receptor, modulate several intracellular events in lymphocytes. A soluble form of CD21 (sCD21) corresponding to the extracellular domain of the receptor circulates in normal plasma. We now demonstrate that purified sCD21 acts as a functional ligand for CD23-expressing monocytes. Soluble CD21 induced an increase in intracellular cGMP levels and the production of IL-6 and TNF-alpha in IL-4-pretreated monocytes induced to express CD23 but not in unstimulated CD23- monocytes. The accumulation of cGMP and the production of TNF-alpha were inhibited by NG-monomethyl-L-arginine (L-NMMA), indicating that sCD21 activates the L-arginine pathway of NO production. We demonstrated that sCD21 activates NO synthase (NOS) since it was found to enhance the conversion of L-arginine into L-citrulline and induce the intracellular expression of inducible NOS in CD23+ monocytes. In addition, sCD21 was shown to up-regulate the expression of HLA-DR and CD40 and decrease that of CD14 on cultured CD23+ monocytes. Thus, in a fashion similar to IgE complexes, sCD21 is able to efficiently trigger CD23 signaling pathways, inducing the release of pro-inflammatory mediators by human monocytes. Soluble CD21 up-regulates the expression of molecules involved in antigen presentation, further suggesting a potential immunoregulatory function for the soluble molecule.

Antigen Presentation↗

PubMed1998

The distribution of IL-13 receptor alpha1 expression on B cells, T cells and monocytes and its regulation by IL-13 and IL-4.

To study the expression of IL-13 receptor alpha1 (IL-13Ralpha1), specific monoclonal antibodies (mAb) were generated. Surface expression of the IL-13Ralpha1 on B cells, monocytes and T cells was assessed by flow cytometry using these specific mAb. Among tonsillar B cells, the expression was the highest on the IgD+ CD38- B cell subpopulation which is believed to represent naive B cells. Expression was also detectable on a large fraction of the IgD-CD38- B cells but not on CD38+ B cells. Activation under conditions which promote B cell Ig class switching up-regulated the expression of the receptor. However, the same stimuli had an opposite effect for IL-13Ralpha1 expression levels on monocytes. While IL-13Ralpha1 mRNA was clearly detectable in T cell preparations, no surface expression was detected. However, permeabilization of the T cells showed a clear intracellular expression of the receptor. A soluble form of the receptor was immunoprecipitated from the supernatant of activated peripheral T cells, suggesting that T cell IL-13Ralpha1 might have functions unrelated to the capacity to form a type II IL-4/IL-13R with IL-4Ralpha.

Animals↗

PubMed1998

Soluble CD21 (sCD21) forms biologically active complexes with CD23: sCD21 is present in normal plasma as a complex with trimeric CD23 and inhibits soluble CD23-induced IgE synthesis by B cells.

A soluble form of CD21 (sCD21) of 135 kDa is spontaneously released by human B and T lymphocytes upon shedding of the extracellular domain of the molecule. By Western blotting, we have now identified two forms of sCD21 of Mr 135 and 90 kDa in normal human serum. We further demonstrate that sCD21 circulates in a complexed form with cleavage fragments of C3 and CD23, two previously identified ligands of the membrane CD21 receptor. The CD23 molecule was in the form of a trimer in the soluble complex purified from plasma by affinity chromatography on anti-CD21 Sepharose. The serum sCD21 complex was also found to contain IgE. The presence of IgE and of CD21 in a soluble complex that contains trimeric CD23 as the only form of soluble CD23 (sCD23) is in agreement with a model in which two of the three lectin heads of CD23 bind to the Cepsilon3 domain of IgE, thus leaving one of the heads available for interaction with CD21. We further demonstrate that sCD21 inhibits sCD23-induced IgE synthesis by IL-4-stimulated B cells. The results indicate that sCD21 in plasma retains the ligand-binding properties of the membrane CD21 receptor and exhibits immunoregulatory properties that may be relevant to allergic and inflammatory disorders.

B-Lymphocytes↗

PubMed1997

Ligation of CD40 activates interleukin 1beta-converting enzyme (caspase-1) activity in vascular smooth muscle and endothelial cells and promotes elaboration of active interleukin 1beta.

Inflammation contributes to a variety of arterial diseases including atherosclerosis. Interleukin 1beta (IL-1beta) in its activated mature 17-kDa form may mediate aspects of vascular inflammation. As shown previously, human vascular wall cells, such as smooth muscle cells (SMC), express the IL-1beta precursor upon stimulation and the IL-1beta-converting enzyme (ICE) constitutively but do not produce mature IL-1beta or express ICE activity. How SMC, the most numerous cell type in arteries, may release active IL-1beta has therefore remained a perplexing problem. We report here that stimulation of human vascular SMC and endothelial cells (EC) through CD40 ligand, a mediator recently localized in human atheroma, induced elaboration of the IL-1beta precursor as well as activation of cell-associated ICE. In addition to the constitutively expressed 45- and 30-kDa immunoreactive ICE proteins, vascular cells incubated with recombinant human CD40 ligand (rCD40L) (but not IL-1 or TNF) showed an increase of a 20-kDa immunoreactive ICE protein by Western blot analysis. Furthermore, SMC and EC stimulated through rCD40L processed recombinant human IL-1beta precursor (pIL-1beta), generating a cleavage product of approximately 17 kDa. Appearance of both the 20-kDa immunoreactive ICE protein and pIL-1beta processing activity required at least 6 h of stimulation with 0.3 or 1.0 microg/ml rCD40L, respectively, and was inhibited by pre-incubation of the ligand with an anti-CD40L antibody. Stimulation of vascular SMC and EC through rCD40L resulted in the release of biologically active IL-1beta, indicating processing of the native IL-1beta precursor induced by the ligand. These findings establish a novel mechanism of IL-1beta activation in human vascular cells and, moreover, indicate a new pathway of ICE-activation, which could participate in inflammatory aspects of atherogenesis and other disease states.

CD40 Antigens↗

PubMed1997

N-acetyl-L-cysteine exhibits antitumoral activity by increasing tumor necrosis factor alpha-dependent T-cell cytotoxicity.

Because of its anticarcinogenic and antimutagenic properties, N-acetyl-L-cysteine (NAC) has been proposed for cancer treatment. Here we present a mechanism of action for NAC in cancer. Our data show that NAC (1) induces an early and sustained increase of membrane tumor necrosis factor alpha (TNF alpha) expression on human stimulated-peripheral blood (PB) T cells and (2) increases membrane TNF-RI and TNF-RII on tumoral cell lines and on T cells after stimulation. These effects result from an early inhibition of both TNF alpha and TNF-R shedding, as well as a later increase of the respective mRNA expression. Consequently, NAC confers cytotoxic properties to human PB T cells through a membrane TNF alpha-dependent pathway. In vivo, NAC given orally inhibits tumor appearance in more than a third (18 out of 50) B6D2F1 mice injected with L1210 lymphoma cells. Spleen cells from protected mice killed L1210 lymphoma cells in vitro in a membrane TNF alpha-dependent manner. Furthermore these mice were resistant to a second inoculation of L1210 cells without further treatment with NAC. Thus, NAC exhibits a potent antitumoral activity by modulating TNF alpha and TNF-R processing without showing any in vitro and in vivo toxicity.

Acetylcysteine↗

PubMed1997

Activation of monocyte/macrophage functions related to acute atheroma complication by ligation of CD40: induction of collagenase, stromelysin, and tissue factor.

BACKGROUND: Plaque disruption with thrombosis commonly causes the acute coronary syndromes. Macrophages, abundant at sites of plaque rupture, release proteinases that weaken plaques and express tissue factor (TF), which initiates thrombosis. The signals that induce expression of these macrophage functions, particularly TF, remain obscure. Recent studies have localized the receptor CD40 and its ligand in human atheroma. This study tested the hypothesis that ligation of CD40 can activate key mononuclear phagocyte functions related to clinical manifestations of atheroma. METHODS AND RESULTS: Stimulation of human monocytes/macrophages through CD40 by either membranes from activated T cells or recombinant CD40L (rCD40L) induced expression of interstitial collagenase, stromelysin, and TF protein and activity. In contrast, the soluble cytokines interleukin-1 or tumor necrosis factor-alpha did not induce or weakly induced TF expression. Neutralization with anti-CD40L antibody markedly inhibited these actions of both T-cell membranes and rCD40L. CONCLUSIONS: By inducing the expression of matrix-degrading proteinases and of TF procoagulant, CD40 signaling may contribute to the triggering of acute coronary events.

Arteriosclerosis↗