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At least 451 records · Page 25Linked to original sources
PubMed2005

A Graves' disease-associated Kozak sequence single-nucleotide polymorphism enhances the efficiency of CD40 gene translation: a case for translational pathophysiology.

We analyzed the mechanism by which a Graves' disease-associated C/T polymorphism in the Kozak sequence of CD40 affects CD40 expression. CD40 expression levels on B cells in individuals with CT and TT genotypes were decreased by 13.3 and 39.4%, respectively, compared with the levels in CC genotypes (P = 0.012). Similarly, Rat-2 fibroblasts transfected with T-allele cDNA expressed 32.2% less CD40 compared with their C-allele-transfected counterparts (P = 0.004). Additionally, an in vitro transcription/translation system showed that the T-allele makes 15.5% less CD40 than the C-allele (P < 0.001), demonstrating that the effect of the single-nucleotide polymorphism (SNP) on CD40 expression is at the level of translation. However, the SNP did not affect transcription, because the mRNA levels of CD40, as measured by quantitative RT-PCR, were independent of genotype. Therefore, our results may suggest that the C allele of the CD40 Kozak SNP, which is associated with Graves' disease, could predispose to disease by increasing the efficiency of translation of CD40 mRNA.

5' Untranslated Regions↗
PubMed2000

IL-4-activated STAT-6 inhibits IFN-gamma-induced CD40 gene expression in macrophages/microglia.

The antagonism between the cytokines IFN-gamma and IL-4 is well documented, but the mechanism by which IL-4 inhibits IFN-gamma-induced gene expression is not clearly understood. CD40 is a type I transmembrane protein that is critical for proper functioning of the immune system. We have previously shown that IFN-gamma is the most potent inducer of CD40 expression by macrophages and microglia. In this report, we describe the molecular mechanisms by which IL-4 inhibits IFN-gamma-induced CD40 expression. IL-4 suppresses IFN-gamma-induced CD40 gene expression in both macrophages and microglia, and such inhibition is dependent on the activation of STAT-6. Nuclear run-on and transfection studies indicate that IL-4-mediated repression is at the transcriptional level. Furthermore, IL-4 inhibition of IFN-gamma-induced CD40 expression is specific, since IL-4 does not inhibit IFN-gamma-induced IFN-responsive factor-1 gene expression. Site-directed mutagenesis studies demonstrate that two STAT binding sites, named proximal and distal IFN-gamma-activated sequences, in the human CD40 promoter are important for IL-4 inhibition of IFN-gamma-induced CD40 promoter activity. Moreover, EMSAs indicate that IL-4-activated STAT-6 binds to these two STAT binding sites. These results suggest that IL-4 inhibition of IFN-gamma-induced CD40 gene expression is mediated by direct STAT-6 binding to the CD40 promoter.

Animals↗
PubMed2001

Characterization of a CD40-dominant inhibitory receptor mutant.

CD40 is an important mediator of immune and inflammatory responses. It is a costimulatory molecule for B cell proliferation and survival. Blockade of CD40 has been shown to induce tolerance and its role in other pathogenic conditions has led to the proposal that CD40 inhibition could be valuable therapeutically. As a first step to this end, we have characterized a CD40-dominant negative receptor. This inhibitory mutant lacks the identified CD40 signaling domains. It inhibits both cotransfected and endogenous CD40 activation of NF-kappaB. This mutant is specific, as it does not affect TNF or latent membrane protein 1 signaling. Its potential usefulness is illustrated by its ability to inhibit the CD40 ligand-stimulated increases of HLA and CD54 expression, molecules involved in Ag recognition and lymphocyte recruitment leading to organ rejection. The inhibitory mutant has no TNFR-associated factor 2-binding capabilities and inhibits the recruitment of TNFR-associated factor 2 to the CD40 signaling complex after stimulation. These studies show that the CD40 inhibitory receptor molecule is effective, specific, and useful both for research and potentially as a clinical tool. And furthermore, it is likely that similar dominant inhibitory receptors can be generated for all of the members of the TNFR superfamily.

Binding Sites↗
PubMed2002

Role of TNF receptor-associated factor 2 in the activation of IgM secretion by CD40 and CD120b.

TNFR-associated factors (TRAFs) participate in the signaling of many TNFR family members, including CD40, CD120a (TNFR1), and CD120b (TNFR2). Previously, we found that a dominant-negative TRAF2 molecule inhibits CD40-mediated Ab secretion by the mouse B cell line CH12.LX. However, disruption of the TRAF2 binding site in the cytoplasmic domain of CD40 does not diminish the ability of CD40 to stimulate Ab secretion, nor is this mutation able to circumvent the inhibition of Ab secretion by dominant-negative TRAF2. Here we demonstrate that CD40-induced TNF stimulates IgM production through CD120b and that CD120b signaling is required for optimal CD40-induced IgM secretion. Furthermore, although both CD40 and CD120b can bind TRAF2, TRAF2-dependent CD40 signals cannot substitute for TRAF2-dependent CD120b signals in the activation of IgM secretion. Our results indicate a potentially important role for CD120b in the activation of IgM secretion and that TRAF2 is used by CD40 and CD120b in distinct ways.

Animals↗
PubMed2002

Suppressor of cytokine signaling 1 inhibits cytokine induction of CD40 expression in macrophages.

CD40 is a type I membrane-bound molecule belonging to the TNFR superfamily that is expressed on various immune cells including macrophages and microglia. The aberrant expression of CD40 is involved in the initiation and maintenance of various human diseases including multiple sclerosis, arthritis, atherosclerosis, and Alzheimer's disease. Inhibition of CD40 signaling has been shown to provide a significant beneficial effect in a number of animal models of human diseases including the aforementioned examples. We have previously shown that IFN-gamma induces CD40 expression in macrophages and microglia. IFN-gamma leads to STAT-1alpha activation directly and up-regulation of NF-kappaB activity due to the secretion and subsequent autocrine signaling of TNF-alpha. However, TNF-alpha alone is not capable of inducing CD40 expression in these cells. Suppressor of cytokine signaling 1 protein (SOCS-1) is a cytokine-inducible Src homology 2-containing protein that regulates cytokine receptor signaling by inhibiting STAT-1alpha activation via a specific interaction with activated Janus kinase 2. Given the important role of CD40 in inflammatory events in the CNS as well as other organ systems, it is imperative to understand the molecular mechanisms contributing to both CD40 induction and repression. We show that ectopic expression of SOCS-1 abrogates IFN-gamma-induced CD40 protein expression, mRNA levels, and promoter activity. Additionally, IFN-gamma-induced TNF-alpha secretion, as well as STAT-1alpha and NF-kappaB activation, are inhibited in the presence of SOCS-1. We conclude that SOCS-1 inhibits cytokine-induced CD40 expression by blocking IFN-gamma-mediated STAT-1alpha activation, which also then results in suppression of IFN-gamma-induced TNF-alpha secretion and subsequent NF-kappaB activation.

Animals↗
PubMed2004

Novel regulatory mechanisms of CD40-induced prostanoid synthesis by IL-4 and IL-10 in human monocytes.

Interleukins IL-4 and IL-10 are considered to be central regulators for the limitation and eventual termination of inflammatory responses in vivo, based on their potent anti-inflammatory effects toward LPS-stimulated monocytes/macrophages and neutrophils. However, their role in T cell-dependent inflammatory responses has not been fully elucidated. In this study, we investigated the effects of both cytokines on the production of PGE(2), a key molecule of various inflammatory conditions, in CD40-stimulated human peripheral blood monocytes. CD40 ligation of monocytes induced the synthesis of a significant amount of PGE(2) via inducible expression of the cyclooxygenase (COX)-2 gene. Both IL-10 and IL-4 significantly inhibited PGE(2) production and COX-2 expression in CD40-stimulated monocytes. Using specific inhibitors for extracellular signal-related kinase (ERK) and p38 mitogen-activated protein kinase (MAPK), we found that both kinase pathways are involved in CD40-induced COX-2 expression. CD40 ligation also resulted in the activation of NF-kappaB. Additional experiments exhibited that CD40 clearly induced the activation of the upstream kinases MAPK/ERK kinase 1/2, MAPK kinase 3/6, and I-kappaB in monocytes. IL-10 significantly inhibited CD40-induced activation of the ERK, p38 MAPK, and NF-kappaB pathways; however, inhibition by IL-4 was limited to the ERK pathway in monocytes. Neither IL-10 nor IL-4 affected the recruitment of TNFR-associated factors 2 and 3 to CD40 in monocytes. Collectively, IL-10 and IL-4 use novel regulatory mechanisms for CD40-induced prostanoid synthesis in monocytes, thus suggesting a potential role for these cytokines in regulating T cell-induced inflammatory responses, including autoimmune diseases.

Antibodies, Monoclonal↗
PubMed2004

CD40 ligation in vivo induces bystander proliferation of memory phenotype CD8 T cells.

Injection of agonistic anti-CD40 Abs into mice has been shown to amplify weak CD8 T cell responses to poorly immunogenic compounds and to convert T cell tolerance to T cell priming. In this study we demonstrate that anti-CD40 treatment of C57BL/6 mice, without Ag delivery, led to a marked increase in the number of memory phenotype CD4 and CD8 T cells. Adoptive transfer experiments using CD40-deficient hosts further revealed that the proliferative response of memory T cells, induced by systemic CD40 signaling, was dependent on CD40 expression of host APCs. CD40 ligation in vivo induced vigorous cell division of both memory phenotype and bona fide virus-specific memory CD8 T cells in a partially IL-15-dependent manner. However, only memory phenotype, but not Ag-experienced memory CD8 T cells increased in cell number after anti-CD40 treatment in vivo. Taken together our data show that activation of APC via CD40 induces a marked bystander proliferation of memory phenotype T cells. In addition, we demonstrate that bona fide Ag-experienced memory CD8 T cells respond differently to anti-CD40-induced signals than memory phenotype CD8 T cells.

Animals↗
PubMed2006

IL-10- and IL-12-independent down-regulation of allergic sensitization by stimulation of CD40 signaling.

Interaction between CD154 (CD40 ligand) on activated T lymphocytes and its receptor CD40 has been shown to be critically involved in the generation of cell-mediated as well as humoral immunity. CD40 triggering activates dendritic cells (DC), enhances their cytokine production, up-regulates the expression of costimulatory molecules, and induces their maturation. It is unknown how stimulation of CD40 during sensitization to an airborne allergen may affect the outcome of allergic airway inflammation. We took advantage of a mouse model of allergic asthma and a stimulatory mAb to CD40 (FGK45) to study the effects of CD40-mediated DC activation on sensitization to OVA and subsequent development of OVA-induced airway inflammation. Agonistic anti-CD40 mAb (FGK45) injected during sensitization with OVA abrogated the development of allergic airway inflammation upon repeated airway challenges with OVA. Inhibition of bronchial eosinophilia corresponded with reduced Th2 cytokine production and was independent of IL-12, as evidenced by a similar down-regulatory effect of anti-CD40 mAb in IL-12 p40-deficient mice. In addition, FGK45 equally down-regulated allergic airway inflammation in IL-10-deficient mice, indicating an IL-10-independent mechanism of action of FGK45. In conclusion, our results show that CD40 signaling during sensitization shifts the immune response away from Th2 cytokine production and suppresses allergic airway inflammation in an IL-12- and IL-10-independent way, presumably resulting from enhanced DC activation during sensitization.

Animals↗
PubMed2004

[Expression of antigen CD40 and survivin gene and their clinical implications in acute myeloid leukemia].

OBJECTIVE: To evaluate the expressions of CD40 antigen and anti-apoptosis gene survivin in acute myeloid leukemia (AML) and their clinical significance. METHODS: By using flow cytometry (FCM) and reverse transcriptase polymerase chain reaction (RT-PCR), CD40 antigen and anti-apoptosis gene survivin mRNA were studied in 48 AML cases and their association with the clinical features of AML was analysed. RESULTS: (1) In the 48 AML cases, positive expression of CD40 antigen was found in 25 cases (52.1%) and positive expression of anti-apoptosis gene survivin mRNA in 35 cases (72.9%). (2) The incidence of splenomegaly, thrombocytopenia and hyperleukocytosis in CD40+ AML cases was significantly higher than those in CD40- AML ones (36.0% vs 8.7%), P=0.025; (72.0% vs 43.5%), P=0.045; (32.0% vs 4.4%), P=0.024. (3) There was no difference in the number of the expression of survivin mRNA between CD40+ AML cases and CD40- AML ones (20/25 vs 15/23) P=0.25, but the expression of survivin mRNA of both the groups was high than those of normal controls (20/25 vs 6/20), P=0.001; (15/23 vs 6/20), P=0.021. In the 48 AML cases the rate of the expression of CD40 antigen was less than those of anti-apoptosis gene survivin mRNA (52.1% vs 72.9%), P=0.041. (4) The complete remission (CR) rate in the survivin+ AML cases receiving chemotherapy was significantly less than that in the survivin- AML ones (31.4% vs 69.2%), P=0.018. CONCLUSIONS: The expression of CD40 antigen might be associated with some unfavorable clinical features of AML. The expression of anti-apoptosis gene survivin might be one of the reasons that AML have a lower CR rate, and it is one of the prognostic factors in AML.

Adolescent↗
PubMedDate not supplied

High CD40 expression in gastric cancer associated with expanding type histology and liver metastasis.

BACKGROUND/AIMS: We have previously reported higher serum TNF-alpha levels in some gastric cancer patients. The status of its receptor (CD40 expression) in gastric cancer tissue and their clinical relevance is worthy of study. METHODOLOGY: The expression of CD40 was examined immunohistochemically in 32 gastric carcinoma specimens and graded as high and low expressions according to the proportion of stained tumor cells. The clinicopathological factors including age, sex, tumor location, size, gross appearance, stromal reaction pattern, degree of cellular differentiation, histological classification, depth of tumor invasion, lymph node status, peritoneal dissemination, liver metastasis and TNM stage were analyzed according to the different expression of CD40. RESULTS: There were 18 patients with low CD40 expression and 14 patients with high CD40 expression. There were more expanding type tumors than infiltrating type by Ming's histological classification (57.1% vs. 16.7%, p=0.027) and liver metastasis (28.6% vs. 0, p=0.028) in the high expression group. The patient survival showed a worse tendency in patients with high CD40 expression, but did not reach statistical difference. There was no correlation between CD40 expression level and other clinicopathological features. CONCLUSIONS: The fact that high CD40 expression existed more in expanding type tumor and had more liver metastasis suggests CD40 may play an important role in local invasion mode and hematogenous spread.

Adult↗
PubMed1994

Involvement of LFA-1/intracellular adhesion molecule-1-dependent cell adhesion in CD40-mediated inhibition of human B lymphoma cell death induced by surface IgM crosslinking.

B cells have been shown to receive negative signals for their growth through crosslinking of surface IgM (sIgM), and it has been demonstrated that anti-IgM Abs induce B cell death. Proliferation of B cells in response to Ag stimulation in vivo may thus require additional signals that inhibit the sIgM-transduced negative signals. Signaling through CD40 has been proposed as a candidate for such costimulatory signals. To investigate the role of CD40-transduced signals in sIgM-mediated B cell death, we used a human B cell line (DND-39) that expresses sIgM, sIgD, and CD40. Crosslinking of sIgM, but not sIgD, by Abs induced DND-39 cell death. The dying cells showed the morphology of apoptosis and DNA fragmentation. Anti-CD40 Abs induced homotypic adhesion of DND-39 cells and rescued them from anti-IgM Ab-induced cell death. Anti-CD40 Abs inhibited anti-IgM Ab-induced cell death when added within 3 h after stimulation with anti-IgM Ab. Treatment with Abs against CD11a, CD18, or CD54 inhibited not only the homotypic adhesion but also the inhibition of anti-IgM Ab-induced apoptosis by anti-CD40 Ab. CD11a antisense decreased the surface CD11a expression, the anti-CD40 Ab-induced homotypic adhesion, and the inhibitory effect of anti-CD40 Ab on anti-IgM Ab-induced apoptosis. The data show that LFA-1/ICAM-1-dependent cell adhesion induced by signaling through CD40 plays an important role in the inhibition of anti-IgM Ab-induced apoptosis of DND-39 cells.

Antigens, CD↗
PubMed1995

Activity of a single-chain immunotoxin that selectively kills lymphoma and other B-lineage cells expressing the CD40 antigen.

We have constructed anti-CD40 immunotoxins consisting of the single chain Fv (sFv) region of the anti-human CD40 mAb G28-5 fused to a truncated form of Pseudomonas exotoxin, PE40. CD40 is an integral membrane glycoprotein found on the surface of B-lineage cells, including lymphomas and leukemias, as well as certain carcinomas. Two forms of the immunotoxin were constructed, one with the light chain variable (VL) region of the sFv preceding the heavy chain variable region (VH) [G28-5 sFv(VL-VH)-PE40] and the second with the sFv in the opposite orientation [G28-5 sFv(VH-VL)-PE40]. Although both forms of G28-5 sFv-PE40 specifically bound to CD40 in ELISAs, the binding of G28-5 sFv(VL-VH)-PE40 was > 10-fold higher. A number of malignant B- and T-cell lines were screened for CD40 expression and susceptibility to G28-5 sFv(VL-VH)-PE40. All of the B-lineage cells tested were CD40 positive and sensitive to the anti-CD40 immunotoxin, with EC50s ranging from 2.5-70 ng/ml, whereas none of the T cell leukemias or lymphomas were antigen positive or were affected by the immunotoxins. Consistent with the antigen-binding results, the VL-VH immunotoxin was > 10-fold more cytotoxic than the VH-VL immunotoxin. The anti-CD40 single-chain immunotoxin fusion protein G28-5 sFv(VL-VH)-PE40 represents a potent and specific cytotoxic agent for the elimination of normal and transformed B-lineage cells expressing CD40.

ADP Ribose Transferases↗
PubMed1994

Agonistic and antagonistic properties of CD40 mAb G28-5 are dependent on binding valency.

CD40 functional responses can be triggered by binding of mAb G28-5. Here we show that G28-5 induces partial CD40 responses and functions as a partial antagonist of natural CD40 ligand, gp39, by preventing gp39 binding. Fab fragments of G28-5 retain inhibitory activity but lose crosslinking-dependent stimulatory activity. The synergistic interaction of CD40 signals with PMA or CD20 show differential requirements for CD40 crosslinking and different sensitivity to cyclosporine A, suggesting that CD40 receptor may use different effector mechanisms for synergy with calcium-dependent CD20 signals or with calcium-independent signals from PMA. Activation of NF-kappa B occurred in RAJI cells by G28-5 or by gp39 treatment, and was CD40 crosslinking-dependent. These results suggest that activation of NF-kappa B is involved in some CD40 receptor signals and may be related to CD40 effects on stimulation or inhibition of apotosis.

Animals↗
PubMed1996

Cytokine activation sensitizes human monocytic and endothelial cells to the cytotoxic effects of an anti-CD40 immunotoxin.

G28-5 sFv-PE40 is a single-chain immunotoxin that is cytotoxic toward malignant B cells expressing CD40. Human monocytes, which also express cell surface CD40, were found to be insensitive to the immunotoxin. Activation of the monocytic cell line THP-1, or freshly isolated peripheral blood monocytes with IFN-gamma, but not IL-3, GM-CSF, IL-6, or TNF-alpha, greatly sensitized the cells toward G28-5 sFv-PE40, lowering the EC50 value from > 10 micrograms/ml to 80 ng/ml. This sensitization could not be explained simply by the two- to threefold increase in cell surface CD40 expression induced by IFN-gamma since TNF-alpha or the combination of TNF-alpha and IL-6 gave similar increases in CD40 expression but did not sensitize the cells to the immunotoxin. Internalization of G28-5 sFv-PE40 after IFN-gamma activation was also increased threefold, reflective of the increase in CD40 expression. IFN-gamma-treated but not -untreated THP-1 cells produced IL-6 and TNF-alpha following incubation with G28-5 sFv-PE40, indicating an association between CD40 signaling, which induces cytokine production, and sensitivity to the immunotoxin. HUVECs also express CD40 but were found to be insensitive to the anti-CD40 immunotoxin. A combination of IFN-gamma and TNF-alpha, but neither cytokine alone, sensitized the endothelial cells to G28-5 sFv-PE40. These data show that activation with cytokines can sensitize monocytes and endothelial cells to an immunotoxin targeted to CD40, most likely by altering the trafficking and/or processing of the immunotoxin after receptor-mediated internalization.

ADP Ribose Transferases↗
PubMed1996

CD40-induced growth inhibition in epithelial cells is mimicked by Epstein-Barr Virus-encoded LMP1: involvement of TRAF3 as a common mediator.

CD40, a member of the tumour necrosis factor receptor family, is expressed on the surface of B lymphocytes where its ligation provides a potent survival signal. CD40 is also expressed in basal epithelial cells and in a number of different carcinomas where its function remains unknown. We observed that contrary to the studies in normal B cells, CD40 ligation in carcinoma cell lines and in normal primary epithelial cells resulted in growth inhibition and enhanced susceptibility to apoptosis induced by anti-neoplastic drugs, TNF-alpha, Fas and ceramide. This effect was also observed in CD40-transfected Rat-1 fibroblasts. The expression of Bcl-2 did not affect growth inhibition induced by CD40 ligation in epithelial cells but the Epstein - Barr Virus-encoded latent membrane protein 1 (LMP1) blocked the effect. Whilst transient expression of LMP-1 resulted in the inhibition of epithelial cell growth, this effect was not observed with a LMP1 mutant lacking the binding domain for TRAF3, a protein which may mediate signal transduction by interacting with the cytoplasmic domains of both CD40 and LMP1. Transient expression of TRAF3 also inhibited epithelial cell growth, whilst expression of a dominant-negative TRAF3 partially blocked the inhibitory effect of CD40 ligation and of transient LMP1 expression. These results suggest that CD40 regulates epithelial cell growth in a manner mimicked by LMP1 and implicate TRAF3 as a common mediator in the transduction of the growth inhibitory signals generated via the CD40 and LMP1 pathways.

Animals↗
PubMed1997

B cells regulate CD40 ligand-induced IL-12 production in antigen-presenting cells (APC) during T cell/APC interactions.

Although stimulation of freshly isolated murine spleen cells with anti-CD3 mAb or Con A failed to generate IL-12 production, the same cell preparations depleted of B cells produced IL-12. Addition of normal B cells inhibited IL-12 production in a cell number-dependent manner. IL-12 production was dependent on the presence of CD4+, but not of CD8+, T cells, and inhibited by addition of anti-CD40 ligand (CD40L) mAb. Anti-CD3 or Con A stimulation induced CD40L expression only on CD4+ T cells, which was inhibited in the presence of B cells. IL-12 production was also induced by interactions between CD40L-transfected Chinese hamster ovary cells and splenocytes depleted of T and B cells, but not of APC, indicating CD40L-induced IL-12 production by APC. The involvement of CD40 molecules was examined by comparing the ability of cells from CD40-deficient (CD40 -/-) and wild-type mice (CD40 +/+) to produce IL-12. Spleen cells from CD40 -/- and CD40 +/+ mice produced comparable amounts of IL-12 in response to bacterial stimuli. However, the B cell-depleted fraction from CD40 -/- mice failed to produce IL-12 when stimulated with anti-CD3 or Con A or when cocultured with CD40L-expressing Chinese hamster ovary cells. These results indicate that CD40L expressed on activated T cells induces APC to produce IL-12 through CD40/CD40L interaction, but this pathway is competitively inhibited by CD40+ B cells incapable of producing IL-12 upon stimulation with CD40L. Thus, this might represent a novel mechanism underlying the regulation of cell-mediated and humoral immunity.

Animals↗
PubMed1996

[CD40 as a mediator of proliferation in normal ans neoplastic thymic epithelium].

AIMS AND METHODS: While CD40 is a costimulatory molecule of utmost importance for B-cell proliferation and Ig class switch its role has not been elucidated in the human thymus and in thymic epithelial tumors. To investigate, whether CD40 is functionally active there, we investigated the proliferative response by 3H-Thymidin incorporation of primary normal and neoplastic thymic epithelial cell cultures to CD40 triggering by soluble CD40 ligand (CD40L). RESULTS: Normal thymic epithelial cells exhibited proliferation in response to CD40 ligand in a dose dependent manner, while a CD40 ligand specific monoclonal antibody prevented this effect. This response was not significantly different from the response of neoplastic thymic epithelial cells derived from myasthenia gravis-associated thymomas. CONCLUSION: Our data demonstrate that CD40 is expressed on the surface of normal and neoplastic epithelial cells of the thymus and is a functional molecule in terms of epithelial cell proliferation in vitro. Given the differential expression of CD40 in the various histological thymoma subtypes in vivo, the finding suggests a role of CD40 in the different mechanisms of tolerance breakdown in thymomas.

Antigens, CD↗
PubMedDate not supplied

CD40 expression in epidermal tumors.

CD40 antigen, expressed on many cell types is involved in cell-cell interactions, with activated T cells expressing the CD40 ligand. In the skin, keratinocytes express CD40 which may play a role in amplifying inflammatory responses. We investigated the expression of this antigen in a series of epidermal tumors in correlation with T cell infiltrates. Our results indicate a-down-regulation or a drastic loss of CD40 antigen by tumor cells from basal cell carcinoma and squamous cell carcinoma and a moderate to discrete CD40 reactivity of keratinocyte from proliferative layers of benign viral-induced lesions. Endothelial cells, most infiltrating cells and a subpopulation of intraepidermal dendritic cells strongly expressed CD40, mainly in benign lesions, in which T cell-keratinocyte interactions may be observed, and were restricted to epithelial cells expressing CD40. The lack of CD40 expression by tumor cells might account for tumor escape mechanism from activated T cells expressing the CD40 ligand.

Antigens, Neoplasm↗