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M Bagot

Publications and source records attributed to M Bagot.

At least 37 records · Page 2Linked to original sources
PubMed2001

CD4(+) cutaneous T-cell lymphoma cells express the p140-killer cell immunoglobulin-like receptor.

Tumor cells of patients with cutaneous T-cell lymphoma (CTCL) have the cell surface phenotype of mature T-helper lymphocytes, and it may be impossible to differentiate them from nonmalignant lymphocytes in skin and blood. Until now, no specific cell membrane marker of CTCL has been reported. In the current study, it is reported for the first time that CTCL cells express the major histocompatibility complex class I binding p140-killer cell immunoglobulin-like receptor, which has been described on a minor subset of natural killer lymphocytes and on a marginal circulating CD8(+) T lymphocyte subset. Interestingly, the molecular characterization of this KIR expressed by CTCL allowed us to isolate a novel allelic form of p140-KIR3DL, resulting in 4 amino acid substitutions, 3 in the extracellular immunoglobulin-like domain of the protein and one in the cytoplasmic region. This finding is likely to be important both for the pathophysiology and for the clinical treatment of patients with CTCL.

Amino Acid Sequence↗
PubMed2001

Functional characterization of neurotensin receptors in human cutaneous T cell lymphoma malignant lymphocytes.

Cutaneous T cell lymphomas are a clonal proliferation of CD4+ T lymphocytes primarily involving the skin. Mycosis fungoides is an epidermotropic CD4+ cutaneous T cell lymphoma, and a more aggressive form, Sezary syndrome, occurs when the malignant cells become nonepidermotropic. The role of neuropeptides in the growth and chemotaxis capacity of cutaneous T cell lymphoma cells remains unknown. In this report, we found that cutaneous T cell lymphoma cells, similarly to normal resting or activated peripheral lymphocytes, were able to bind neurotensin. We used an interleukin-2-dependent cutaneous T cell lymphoma malignant T cell line derived from cutaneous T cell lymphoma lesions in order to study the role of neurotensin in the proliferation and migration of these malignant cells. First, we determined that the malignant cells expressed neurotensin receptors on their cell membrane. Functional results indicated that neurotensin did not stimulate the growth of the cell line. In contrast, this neuropeptide inhibited the proliferation of the tumor cells in response to exogenous interleukin-2. Furthermore, we found that neurotensin enhanced both spontaneous and chemoattractant-induced migration of the malignant cells. This suggests that neurotensin in skin can play a role in the disease by locally limiting the growth of the cutaneous T cell lymphoma tumor cells in response to cytokines and by enhancing their chemotaxis capacity.

CD4-Positive T-Lymphocytes↗
PubMed2001

Increased expression of a novel early activation surface membrane receptor in cutaneous T cell lymphoma cells.

Using a newly generated monoclonal antibody we identified the 96 kDa transmembrane receptor SC5 expressed simultaneously on a human Sezary cell line and a minor T cell subset in normal individuals. SC5 antigen was detected mostly on CD45RO+ lymphocytes from both CD4+ and CD8+ subsets as well as on natural killer and B lineage cells. SC5 surface expression increased very early after polyclonal stimulation of CD3+ cells due to the transfer of intracellular SC5 molecules to the cell membrane. Engagement of SC5 receptor by its monoclonal antibody inhibited the anti-CD3-induced proliferation and cytokine secretion of peripheral blood T cells and cell clones, whereas SC5 monoclonal antibody did not affect the cytotoxic activity of CD8+ T cell clones. Extensive phenotypic analysis revealed that the percentage of SC5+ CD4+ circulating lymphocytes in Sezary syndrome patients was significantly increased in comparison with controls (p < 0.01) and correlated with the morphologically detected percentage of Sezary syndrome cells in peripheral blood (p < 0.001). In one patient we clearly demonstrated that the circulating malignant T cells coexpress SC5 molecules. Importantly, ligation of SC5 receptor in a cutaneous T cell lymphoma cell line profoundly inhibited the anti-CD3-induced proliferation. Consequently, the expression of SC5 receptor in the peripheral blood of Sezary syndrome patients may serve not only to detect the presence of circulating malignant CD4+ cells but also as a target for immunotherapy.

Antibodies, Monoclonal↗
PubMed2001

Erythrodermic cutaneous T-cell lymphoma with disseminated pustulosis. Production of high levels of interleukin-8 by tumour cells.

Interleukin (IL) -8 is a neutrophil chemoattractant cytokine with proinflammatory and growth-promoting activities, which is involved in the pathogenesis of several inflammatory diseases. It is found in high amounts in lesional biopsies of pustular diseases such as psoriasis and palmoplantar pustulosis. We report a 50-year-old woman with a 10-year history of erythroderma with disseminated pustulosis. Skin biopsies showed an epidermotropic infiltrate composed of atypical CD4+ CD8+ lymphocytes with numerous admixed neutrophils. Peripheral blood flow cytometric analysis revealed a major clonal subset of CD3+ CD4+ CD8+ T-cell receptor Vbeta22+ atypical lymphocytes. Bone marrow biopsy, lymph node biopsy and computed thoracoabdominal tomography were normal. Serologies for human T-cell lymphotropic virus type I and human immunodeficiency virus were negative. Our patient's status deteriorated despite topical (nitrogen mustard, psoralen plus ultraviolet A) and systemic (interferon, methotrexate, multiagent chemotherapy) treatments, and she finally died. We showed that our patient's peripheral blood lymphocytes (PBL) spontaneously produced high amounts of IL-8. In contrast, PBL of patients with classical Sézary syndrome produced lower amounts of IL-8. The production of IL-8 by tumour T cells could explain this unusual clinical and histopathological presentation of cutaneous T-cell lymphoma as disseminated pustulosis.

Dermatitis, Exfoliative↗
PubMed2001

Crosstalk between tumor T lymphocytes and reactive T lymphocytes in cutaneous T cell lymphomas.

We have established several tumor T cell lines, both from the skin and from the blood of a patient with an MHC class II-/class I+, CD4+ cutaneous T cell lymphoma (CTCL). These cell lines, like the initial tumor cells, had a CD3+CD4+CD8- phenotype. We also isolated two cytotoxic T lymphocyte clones from the tumor site of this CTCL patient. These clones displayed a CD4+CD8dim+ (TC5) and CD4+CD8- (TC7) phenotype and mediated a specific MHC class I-restricted cytotoxic activity toward noncultured tumor cells and autologous tumor cell lines. Despite surface expression of Fas on tumor cells and Fas-L induction on TC5 and TC7 cell membrane after coculture with autologous tumor cells, the CD4+ CTL clones did not use this cytotoxic mechanism to lyse their specific target. TC7 used a granzyme/perforin-dependent pathway, whereas TC5 used a TRAIL-dependent mechanism. Quantitative analysis of cytokine mRNA expression indicated that while the tumor cells displayed a Th2-type profile, the CTL clones expressed Th1-type cytokines. Preincubation of TIL clones with autologous tumor cells in a short-term culture induced their activation and subsequent amplification of the Th1-type response, which indicates a direct contribution of the malignant cells in the Th1/Th2 imbalance. However, we found that tumor cells produced high amounts of TGF-beta, which could explain the inhibition of a specific antitumor immune response. Another mechanism to avoid the host immune response was the expression of CD158a, CD158b, p70, and CD94/NKG2A inhibitory receptors by tumor-specific lymphocytes. Finally, we present recent data on new antigen structures expressed both by long-term CTCL lines and uncultured tumor cells.

Antigens, Neoplasm↗
PubMed2000

Diagnostic value of dominant T-cell clones in peripheral blood in 363 patients presenting consecutively with a clinical suspicion of cutaneous lymphoma.

It is now widely accepted that polymerase chain reaction (PCR) analysis of cutaneous T-cell clonality is of diagnostic value in cutaneous T-cell lymphomas (CTCLs) and most helpful in the diagnosis of mycosis fungoides (MF). However, the diagnostic and prognostic value of circulating clonal T cells remains unclear. We studied T-cell clonality in the peripheral blood (PB) and the cutaneous lesion, sampled at the same time, in 363 consecutively seen patients with a clinical suspicion of cutaneous lymphoma. Using a PCR technique providing a specific imprint of T-cell clones (PCRgamma-denaturing gradient gel electrophoresis), we found that detection of identical circulating and cutaneous T-cell clones was associated with the diagnosis of CTCL (P <.001). Detection of circulating tumor cells in patients with MF was infrequent (12.5%), except in those with erythrodermic MF (42%; P =.003). Moreover, among the 46 patients who had identical circulating and cutaneous T-cell clones, 25 (56%) had erythroderma. The finding of a dominant clone in the PB but not in the skin was frequent, regardless of the clinicohistologic classification; it occurred in 30% of patients with CTCL, 41% with non-CTCL malignant infiltrates, and 34% with benign infiltrates. This pattern was significantly more frequent in patients over 60 years of age (P <.002), even in the CTCL group (P <. 01). In conclusion, dominant T-cell clones detected in the PB of patients with MF by using a routine PCR technique are rarely tumoral and are more often related to age. A multicenter prospective study is under way to establish the prognostic value of circulating tumor cells.

Adult↗
PubMed2000

Functional characterization of an IL-7-dependent CD4(+)CD8alphaalpha(+) Th3-type malignant cell line derived from a patient with a cutaneous T-cell lymphoma.

CDR3 of the functional rearranged T-cell receptor variable beta region (TCR-Vbeta) transcript was sequenced in order to demonstrate for the first time the identity between a long-term cultured T-cell line derived from a cutaneous T-cell lymphoma (CTCL) patient and the malignant T-cell clone present in the blood. The patient's peripheral blood lymphocyte-derived cultured T-cell line had a CD3(+)Vbeta22(+)CD4(+)CD8alphaalpha(+)CD25(-) phenotype. It was named Pno and had been cultured for more than 1 year. Both fresh and long-term-cultured tumor cells proliferated highly in response to interleukin-7 (IL-7), and exogeneous IL-7 prevented Pno lymphocytes from apoptosis and maintained high levels of Bcl-2 expression. This unique malignant cloned lymphocyte line was further used to carry out functional studies. The results indicated that the CD3/TCR structures expressed by the Pno lymphocytes were functional because an immobilized anti-CD3 monoclonal antibody (mAb) or the combination of a soluble anti-CD3 mAb with submitogenic doses of phorbol 12 beta-myristate 13 alpha-acetate induced a proliferative response. Further, the CD2 and CD28 coreceptors were functional because they were able to induce a strong proliferative response upon their specific stimulation. Finally, the Pno T cell line had a Th3-type cytokine profile because it produced high amounts of the immunosuppressor cytokine tumor growth factor-beta1 (TGF-beta1). This high production of TGF-beta1 may inhibit antitumor specific responses in CTCL.

CD4 Antigens↗
PubMed2000

Transformation of mycosis fungoides: clinicopathological and prognostic features of 45 cases. French Study Group of Cutaneious Lymphomas.

The course of mycosis fungoides (MF) is indolent except when transformation to a large T-cell lymphoma occurs. The diagnosis of transformed MF (T-MF) relies on the presence of more than 25% of large cells on biopsy of an MF lesion. We analyzed 45 patients with T-MF recorded by the French Study Group on Cutaneous Lymphomas to better determine clinicopathological features of MF transformation and to analyze their impact on prognosis. Median time from diagnosis of MF to transformation was 6.5 years. Extracutaneous progression was present in 20 patients. Mean survival from transformation to death was 22 months. In univariate analysis, only an extracutaneous progression was associated with a worse prognosis (5-year actuarial survival: 7.8% versus 32%). Neither sex, age, clinical and skin disease stage at transformation, transformation speed, nor percentage of large cells or CD30 expression (14 of 45) had a prognostic value. When performing multivariate analysis, age (at least 60 years), and extracutaneous spreading were found to be associated with a poor prognosis. There was no difference between survival curves of patients with T-MF and with pleomorphic large T-cell CD30- lymphomas. The main diagnostic pitfall was "histiocytic-rich" MF, requiring CD68 staining for the diagnosis of T-MF. Out of 45 patients, 6 presented an histologic transformation before clinical progression, suggesting that an early histopathological diagnosis may be performed by histological follow-up. The prognostic value of such early histopathological diagnosis must be confirmed by prospective studies.

Adult↗
PubMed2000

Cutaneous involvement in patients with angioimmunoblastic lymphadenopathy with dysproteinemia: a clinical, immunohistological, and molecular analysis.

OBJECTIVE: To determine whether cutaneous involvement in patients with angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is related to a clonal T-cell proliferation. DESIGN: Retrospective study. SETTING: University hospitals. PATIENTS: Ten patients with AILD and cutaneous involvement. MAIN OUTCOME MEASURE: The T-cell receptor-gamma (TCRG)gene rearrangement was studied with the use of polymerase chain reaction and denaturing gradient gel electrophoresis in blood, nodal, and skin samples. Skin and nodal samples were investigated also for the presence of Epstein-Barr virus (EBV) RNA by in situ hybridization. RESULTS: A transient morbilliform eruption of the trunk was seen most often. Other cutaneous features were infiltrated plaques and purpuric or urticarial lesions. A clonal TCRG gene rearrangement was detected in 7 skin samples, corresponding to a maculopapular eruption with a histological pattern of nonspecific mild lymphoid dermal infiltrate in 6 patients, and to erythematous plaques with histological findings of typical cutaneous lymphoma in 1 patient. In the 5 patients in whom a TCRG gene rearrangement was evidenced in skin and lymph node samples, identical clones were detected in both. Five patients died by the end of the study, with a mean survival of 33.2 months. Four of these 5 patients had a clonal infiltrate in skin and lymph nodes. The EBV RNA was detected in only 1 of 10 skin biopsy specimens and in 5 of 8 lymph nodes tested. CONCLUSIONS: Cutaneous involvement is often related to a clonal T-cell proliferation in AILD, even when clinical and histological features are nonspecific. Cutaneous infiltrate seems to be clonally related to the nodal T-cell proliferation. The role of EBV infection in skin lesions was not evidenced.

Adult↗
PubMed2000

Triggering CD101 molecule on human cutaneous dendritic cells inhibits T cell proliferation via IL-10 production.

Since the CD101 molecule is expressed on a major subpopulation of HLA-DR(+), CD1a(+), CD1c(+) cutaneous dendritic cells (DC), we studied the functional role of CD101 on cutaneous DC. Anti-CD101 monoclonal antibody (mAb) inhibited the proliferation of T cells induced by cutaneous DC. There was a synergistic inhibition between anti-CD101 mAb and anti-CD86/anti-CD80 mAb. Anti-CD101 mAb exerted its inhibitory effect when binding to the CD101 expressed on cutaneous DC. No positive role of CD101 putative ligand expressed by T cells in T cell proliferation was demonstrated, as T cells proliferated in response to soluble anti-CD3 mAb in the presence of CD86-transfected cells but not in the presence of CD101-transfected cells. Of major significance is the fact that IL-10 was produced by cutaneous DC after CD101 triggering with anti-CD101 mAb, while IL-10 secretion was up-regulated in mixed cutaneous DC-T cell cultures after CD101 triggering. Furthermore, IL-10-neutralizing mAb could reverse the inhibition induced by anti-CD101 mAb. Our results demonstrate that the CD101 triggering on cutaneous DC inhibits T cell proliferation via IL-10 production, suggesting an important regulatory role played by the CD101 molecule on DC during T cell activation.

Animals↗
PubMed2000

Primary cutaneous large B-cell lymphomas.

According to the European Organization for Research and Treatment of Cancer classification, primary cutaneous large B-cell lymphomas are subdivided into 2 groups: follicle center cell large B-cell lymphomas and large B-cell lymphomas of the leg. The first type predominantly affects middle-aged adults with an equal gender distribution and presents with lesions on the head and trunk. Histology shows proliferations of predominantly large cleaved cells. The prognosis is excellent, with a 5-year survival rate >90%. The second group predominantly affects elderly females. Histologically the lesions are composed of centroblasts and/or immunoblasts (large round cells). The prognosis is more unfavorable with a 5-year survival rate of 50%. Intravascular large B-cell lymphoma is still classified as a provisional entity.

Age Distribution↗
PubMed2000

Leucoderma associated with flares of erythrodermic cutaneous T-cell lymphomas: four cases. The French Study Group of Cutaneous Lymphomas.

We describe four patients with erythrodermic cutaneous T-cell lymphomas (two with erythrodermic mycosis fungoides, and two with Sézary syndrome) who presented with extensive hypopigmented lesions that occurred during flares of their cutaneous disease. These cases must be distinguished from previously described hypopigmented mycosis fungoides where hypopigmented lesions were the sole manifestation of the lymphoma. In two cases a biopsy was performed on hypopigmented skin, showing an infiltrate of atypical lymphocytes with epidermotropism and absence of melanocytes, as in vitiligo. It is suggested that the hypopigmentation could be due to the cytotoxicity of tumour or reactional lymphocytes directed against melanocytes.

Aged↗
PubMed2000

Blister fluid T lymphocytes during toxic epidermal necrolysis are functional cytotoxic cells which express human natural killer (NK) inhibitory receptors.

Toxic epidermal necrolysis (TEN) is a rare life-threatening adverse drug reaction characterized by a massive destruction of the epidermis. Immunohistological studies of skin biopsies of TEN showed infiltrates of predominantly CD8+ T lymphocytes even though other authors reported a prominent involvement of cells of the monocyte-macrophage lineage. The aim of this study was to characterize phenotypically and functionally the cells present in the cutaneous blister fluid of four patients with TEN. We first determined that lymphocytes were predominant in blister fluid obtained early, while monocytes/macrophages later became the most important population. We then showed that this lymphocyte population, mainly CD3+CD8+, corresponded to a peculiar cell subset as they expressed cutaneous leucocyte antigen, killer inhibitory receptors KIR/KAR and failed to express CD28 molecule. Functionally, we determined that blister T lymphocytes had a cytotoxic T lymphocyte (CTL)- and NK-like cytotoxicity. The role of this cytotoxic lymphocyte population present at the site of lesions during TEN remains to be understood.

Adult↗
PubMed2000

Primary CD30-positive cutaneous T-cell lymphomas and lymphomatoid papulosis frequently express cytotoxic proteins.

AIMS: To analyse the relationship between expression of cytotoxic proteins, histopathology and the CD30 status in primary cutaneous T-cell disorders, we investigated the expression of TIA-1, granzyme B and perforin in CD30 negative and CD30 positive cutaneous T-cell lymphomas (CTCL) and lymphomatoid papulosis (LP). METHODS AND RESULTS: We studied 26 cases of CTCL and 12 cases of LP for the expression of TIA-1, granzyme B and perforin which are granule-associated proteins of cytotoxic lymphocytes involved in the mechanism of apoptosis. We showed that most cases (10/13) of CD30 negative pleomorphic lymphomas expressed cytotoxic proteins only in scattered, apparently reactive lymphocytes, the exception being one CD8+ CTCL and two gammadelta subcutaneous 'panniculitis-like' T-cell lymphomas. We also showed that at least one cytotoxic protein was expressed in a proportion of neoplastic cells in 77% (10/13) of CD30+ T-cell lymphomas (3/4 pleomorphic and 7/9 anaplastic) and in a proportion of atypical cells in 75% (9/12) of LP. CONCLUSIONS: Our findings show a strong correlation between the CD30 phenotype and the expression of cytotoxic proteins in primary CTCL. In addition, these results provide further evidence for an overlap between lymphomatoid papulosis and cutaneous CD30+ pleomorphic and anaplastic lymphomas. These entities, which belong to the spectrum of CD30 positive cutaneous T-cell lymphoproliferations, appear to be derived from cytotoxic cells.

CD4 Antigens↗
PubMed2000

CD101 expression by Langerhans cell histiocytosis cells.

AIMS: Our objective was to study the expression of a recently identified cell surface molecule, CD101 and in Langerhans cell histiocytosis (LCH) patients as CD101 has been shown to be present on dendritic cells. We wanted to determine if CD101 expression could be helpful for the diagnosis of LCH in conjunction with other markers (CD1a, S100 protein), and could be predictive of the evolution and dissemination of the disease. METHODS AND RESULTS: The expression of CD101 was studied by immunohistochemical technique in 11 cases of Langerhans cell histiocytosis on frozen sections. The expression of CD101 was positive in nine cases, high in six cases and low in three cases. There was no expression in the other two cases. No correlation with the evolution, the localization or the dissemination of the disease could be evidenced. CONCLUSIONS: CD101 is a new phenotypic marker that might be useful in combination with other markers for the diagnosis of LCH. However, as the anti-CD101 antibody works only in frozen sections, its value is limited compared to anti-CD1a antibody.

Antigen Presentation↗