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C Blanc

Publications and source records attributed to C Blanc.

At least 19 recordsLinked to original sources
PubMed1996

Complete TCR-delta rearrangements and partial (D-J) recombination of the TCR-beta locus in CD34+7+ precursors from human cord blood.

In the neonatal human thymus, early immature precursors co-express CD34 and CD7 cell surface Ags, and we have recently shown that its most primitive CD34+7+1- fraction includes TCR-beta-rearranging cells. Bone marrow and cord blood also contain a CD34+7+ population. Although this population is heterogeneous in terms of both phenotype and differentiation capacities, it may include T cell-committed thymus colonizing precursors (prothymocytes). Recently, it has been shown in the mouse that initiation of TCR-beta rearrangements is not restricted to early thymocytes. In the present study, we examined the TCR-beta and TCR-delta rearrangement and transcription status of cord blood CD34+7- and CD34+7+ subpopulations. RNA and DNA were isolated from these cell subsets purified by two consecutive rounds of fluorescence-activated cell sorting from CD3-depleted cord blood cells. Using D-J(beta) or V-J(beta) primer sets and genomic DNA PCR amplification, we showed that CD34+7+, but not CD34+7-, contained D-J(beta) rearrangements without concomitant V-D(beta) recombination. These partial TCR-beta rearrangements within CD34+7+ progenitors were also confirmed at the transcriptional level. Furthermore, whereas none of the CD34+ cord blood cell fraction expressed TCR-alpha transcripts, mature V(delta)1-C(delta) mRNA could be amplified from the CD34+7+ subset. The TdT gene was also transcriptionally active in CD34+7+ cells, thus confirming their lymphoid progenitor content. These data indicate that cord blood CD34+7+ cells, like CD34+7+1- neonatal thymocytes, can initiate TCR-beta gene recombination, reinforcing the idea that T cell commitment may occur before prothymocyte migration to the thymus.

Animals↗
PubMed1995

Early human thymocyte proliferation is regulated by an externally controlled autocrine transforming growth factor-beta 1 mechanism.

Early thymocytes undergo extensive proliferation after their entry into the thymus, but cellular interactions and cytokines regulating this intrathymic step remain to be determined. We analyzed the effects of various T-cell growth factors and cellular interactions on in vitro proliferation of early CD2+CD3/TCR-CD4-CD8- (triple negative [TN]) human thymocytes. Freshly isolated TN cells were then assayed for their growth capacity after incubation with CD2I+III-monoclonal antibody (MoAb), recombinant human interleukin-2 (IL-2), IL-7, and/or IL-4. These cells displayed significant proliferative responses with IL-4, IL-7, or CD2-MoAb+IL-2. The addition of recombinant transforming growth factor beta (TGF beta) or autologous irradiated CD3+CD8+CD4- cells to TN cell cultures dramatically decreased their growth responses to IL-2 and IL-7, whereas IL-4-induced proliferation was less sensitive to growth inhibition. We thus asked whether the CD8+ cell-derived inhibitory effect was due to TGF beta. The addition of neutralizing anti-TGF beta MoAb completely abolished CD8+ cell-derived inhibition of TN cell growth. Analysis of CD8+ cell-derived supernatants indicated that these cells had low TGF beta 1 production capacity, whereas TN cells secrete significantly high levels of TGF beta 1. Cell fixation studies showed that TN cells were the source of the TGF beta. TGF beta 1 released from TN cells was in the latent form that became the active inhibitory form through interaction of TN cells with CD8+ cells. Together, these data suggest a role for TGF beta 1 as an externally controlled, autocrine inhibitory factor for human early thymocytes, with a regulatory role in thymic T-cell output.

CD4 Antigens↗
PubMed1995

A Th0/Th2-like function of CD4+CD7- T helper cells from normal donors and HIV-infected patients.

We previously reported the expansion during HIV infection of a subset of CD4+ T cells characterized by a lack of CD7 cell surface expression. This CD4+CD7- subset showed in normal donors a lower cell proliferation than CD4+CD7+ autologous cells after CD3 triggering or CD28 costimulation. Our aim was to further characterize the Th function of this CD4+CD7- T cell subset, both in normal donors and in HIV-infected patients. Their CD4+CD7- cell proliferation and cytokine secretion were analyzed after cell-sorting and co-stimulation of the CD3 and CD28 pathways. In normal donors, the IL-2 produced by CD4+CD7- cells in response to a CD3 plus CD28 costimulus represented 50 +/- 28% of the autologous CD4+CD7+ cell IL-2 secretion. In addition, the CD4+CD7+ T cells produced higher amounts of IL-4 and IL-10 than the CD4+CD7+ cells with mean CD4+CD7-: CD4+CD7+ ratios of 5.4 +/- 4.5 and 26 +/- 25, for IL-4 and IL-10, respectively, whereas the IFN-gamma production was similar in both subsets. After a triggering of the CD3 complex alone, significant amounts of IL-2 were detectable in CD4+CD7+ cell supernatants only; conversely, IL-4 and IL-10 could be detected only in the culture medium from CD4+CD7- T cells. This profile of cytokine production was maintained both over time and at the clonal cell level in the CD4+CD7- T cell subset. In HIV-infected patients, the CD4+CD7- T cell expansion observed in relationship with disease progression was associated to an in vivo activation of the CD4+CD7- cells, as assessed by cell surface expression of the HLA-DR, CD25, CD71, and CD57 markers. The CD4+CD7- T cells from HIV-seropositive patients showed the same imbalance of cell proliferation and IL-2, IL-4, and IL-10 production as observed in normal donors despite low levels of proliferation and cytokine production. Together, our data indicate that the lack of CD7 expression defines a CD4+ Th cell subset with a Th0/Th2-like profile of cytokine secretion in normal individuals. The CD4+CD7- subset is expanded during HIV infection and characterized by the same although impaired profile of cytokine production. These CD4+CD7- T cells might play a role in the Th cell dysfunctions observed in HIV infection.

Antigens, CD↗
PubMed1995

CD34-positive early stages of human T-cell differentiation.

Thymus, the main organ for T lymphopoiesis, requires a permanent influx of progenitors from bone marrow (BM) or fetal liver. An essential question relating to early T-cell development is the identification of the progenitor population which actually homes to the thymus. Recent findings have shown that human multipotent progenitor/stem cells expressing CD34 have the capacity to differentiate into T cells when introduced into a thymic environment. More mature CD34+ bone marrow cells coexpressing CD7 and having a poor myeloid differentiation capacity can also efficiently differentiate into T cells in vitro. These lymphoid committed precursors might be the true thymic repopulating cells. In the thymus, cells with a similar CD34+7+ phenotype include the most primitive thymocyte precursors. CD34+ thymocytes have no myeloid differentiation potential, but may include precursors for natural killer (NK) cells. Interleukin-7 (IL7) is a potent in vitro growth factor for CD34+ thymocytes. Whereas current data do not support a crucial role for IL2, patients with IL2 receptor gamma chain (IL2R gamma) deficiency lack T- and NK cells. The recent demonstration that IL2R gamma is part of the receptor for IL7 strongly suggests that this cytokine plays an essential role in in vivo T lymphocyte and NK development.

Animals↗
PubMed1994

Maturation of acute T-lymphoblastic leukemia cells after CD2 ligation and subsequent treatment with interleukin-2.

In this study, we have investigated the ability of various cytokines to induce the maturation of acute lymphoblastic leukemia (T-ALL) cells with early T-cell phenotype. Leukemic blasts from 17 untreated T-ALL patients were assayed for their ability to acquire mature T-cell markers, CD3/T-cell receptor (TCR) in particular, after incubation with one or a combination of recombinant human interleukin-1 (IL-1), IL-2, IL-4, IL-7, and CD2-specific monoclonal antibody (MoAb). IL-7 or IL-2 induced the proliferation of some leukemic cells, whereas sequential cell treatment with CD2-MoAb and then IL-2 promoted CD3/TCR expression on nearly all CD2+ cells (15 of 16), except for 1 T-ALL that developed into CD3-CD16+CD56+ cells. Differentiation of T-ALL cells was also evidenced through the downregulation of CD34 precursor cell antigen, the generation of CD4+ and CD8+ cells from CD4+ CD8+ precursors, and the acquisition of mature T-cell functions. CD2 ligation induced a progressive increase of surface expression of IL-2 receptor alpha (IL-2R alpha) and IL-2R beta and an accelerated in vitro death of leukemic cells. The ligation of IL-2R by IL-2 rescued T-ALL cells from death and promoted their progression toward more mature cells expressing extracellular CD3/TCR alpha beta complexes. Intracellular analysis indicates that TCR alpha transcription and membrane translocation of both TCR alpha and TCR beta were promoted in these conditions. Analysis of intracellular signals transduced during T-ALL differentiation indicated that CD2-ligation induced Ca2+ influx and that the ligation of CD2 and IL-2R induced distinct tyrosine phosphorylation patterns. The addition of inhibitors of tyrosine phosphorylation abolished T-ALL cell differentiation, which suggests the involvement of tyrosine kinases in this phenomenon. Together, we showed the constant maturation of leukemic early T cells after stimulation of surface CD2 and the high-affinity IL-2R.

Antibodies, Monoclonal↗
PubMed1994

Early cytoreduction: a major prognostic factor in adult acute lymphoblastic leukemia.

Prognostic factors in acute lymphoblastic leukemia (ALL) are used for treatment stratification of ALL. Definition of simple parameters such as the presence or absence of peripheral leukemic cells after one week of treatment could help for stratification. A retrospective study was conducted on 79 previously untreated adult patients with ALL followed in the Hematology department of Hotel Dieu from 1981 to 1991. 84% of patients achieved complete remission (CR), 7% were refractory to induction treatment, and 7 patients (9%) died during the first month after diagnosis. After multivariate analysis the only independent statistically significant factors for achieving CR were the absence of peripheral blast cells at day 7 (PBC D7) (p = 0.009) and age (< 50 years) (p = 0.03). For CR duration the same independent statistically significant factors were found (PBC D7 = 0 versus > 0, p = 0.008; and age < or > or = 30 years, p = 0.045). The PBC D7 value was more significant when circulating blast cells were present at diagnosis. In patients with more than 50,000 PBC at diagnosis, the 10- years event free disease was 62% +/- 20% when PBC were absent at day 7 versus 0% when PBC were present (p < 0.002). All 20 patients with prolonged DFS had PBC D7 = 0 achieving CR by 28 days. The persistence of PBC at Day 7 could be used as a factor to identify a subgroup of poor prognosis adults with ALL.

Adolescent↗
PubMed1994

[Phenotypic and functional characterization of human prothymocytes].

We report herein the phenotypic and functional analysis of human bone marrow and thymus derived early T cells. Commitment to T cell lineage is acquired during CD7 antigen expression by CD34+ precursors in human bone marrow and before thymus colonization. Early thymocytes show similar phenotypic characteristics as bone marrow T cells. They rapidly acquire CD4 before the dual expression of CD4 and CD8. Their expansion and differentiation is regulated by two major factors: thymic stroma and cytokines produced by these stroma cells or by thymocytes themselves. Among cytokines, IL1 and sCD23 produced by thymic epithelial cells support in vitro early T cell development.

Adult↗
PubMed1993

CD34-expressing human thymocyte precursors proliferate in response to interleukin-7 but have lost myeloid differentiation potential.

CD34 is a marker for pluripotent stem cells also present on lineage-committed hematopoietic progenitors from bone marrow and a subpopulation of immature thymocytes. To characterize these early immature thymocytes, we have studied 24 pediatric thymus samples for CD34/7 expression. Three subpopulations could be defined from these T-cell receptor (TcR-) immature thymocytes: CD34+7++ (12.0 +/- 5.8), CD34-7++ (12.6 +/- 8.6), and CD34-7+ (71.5 +/- 17.0%). CD7++ represents upregulation of this antigen and is expressed by cells of a blast-like morphology. Three-color flow cytometric analysis of these three subsets suggests the following ordered differentiation sequence: CD34+7++1-4-8-45RA+-->CD34+7++1+ 4+8-45RA+/- -->CD34-7++1+4+8-+45RO+-->CD34-7+1++4+8+45RO+. Early immature thymocyte cell division is essential in the thymus to generate a large number of precursors before the initiation of the selection process. We observed that both CD2 as well CD28 activation pathways were inefficient to serve as costimulant with phorbol ester 12-O-tetradecanoyl phorbol 13-acetate or interleukin-2 (IL-2) to induce the proliferation of the three CD34/7 subsets isolated by cell sorting. However, whereas IL-1, IL-2, IL-3, IL-4, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor were ineffective, IL-7 was a potent cytokine, alone or in synergy with stem cell factor (SCF) to induce immature thymocyte proliferation. The proliferation induced by IL-7 or IL-7 + SCF is restricted to the CD34+ cells and, after 4 or 8 days of culture with IL-7, some CD34+7++ acquire the expression of CD4 and/or CD8, but remain CD3/TcR-. We also tested the myeloid differentiation capacity of these CD34 immature thymocytes. Using two different approaches, myeloid colony formation in methylcellulose and limiting dilution analysis in the presence of myeloid growth factors, we were unable to detect myeloid differentiation capacity from CD34+ early thymocytes, whereas CD34+7+ from bone marrow contained about 10% of the clonogenic cells present in the CD34+7- fraction. Together, these data support the concept that thymic CD34+7++ represents the earliest thymic subset of fully committed T-lineage cells, capable of proliferating specifically to IL-7.

Antibodies, Monoclonal↗
PubMed1993

Post-transfusional anti-HCV-negative, non-A, non-B hepatitis. (I) a prospective clinical and epidemiological survey.

Despite the identification of hepatitis C virus (HCV) and the detection of anti-HCV antibodies in the serum of infected individuals, a sizeable proportion of patients who develop transfusion-associated acute non-A, non-B hepatitis following surgery do not develop anti-HCV antibodies. The cause of this disease remains unknown. To assess the role of homologous blood transfusion in anti-HCV-positive and -negative, non-A, non-B hepatitis following surgery, patients receiving homologous blood, autologous blood alone, or no transfusions were prospectively studied. Consumption of potentially hepatotoxic drugs was also quantified. Anti-HCV antibodies were tested retrospectively when commercial assays became available. Of the 181 patients who received homologous blood which tested negative for surrogate markers of infectivity, 19 (10.5%) developed non-A, non-B hepatitis, associated with anti-HCV seroconversion in three cases. Of the 90 autologous blood recipients, non-A, non-B hepatitis developed in one (1.1%), who did not seroconvert to anti-HCV. Of the 64 untransfused patients, non-A, non-B hepatitis developed in one (1.6%), who was anti-HCV-positive before surgery. Logistic regression analysis showed that the occurrence of non-A, non-B hepatitis was associated with homologous blood transfusion, but not with the consumption of potentially hepatotoxic drugs. The 16 homologous-blood recipients who developed anti-HCV-negative, non-A, non-B hepatitis had received blood from 70 donors, none of whom had detectable anti-HCV antibodies but six of whom had minimal elevations of serum aminotransferase activity. Anti-HCV-negative, non-A, non-B hepatitis is mainly transfusion-transmitted in the surgical setting. Known hepatotropic agents may be involved despite the absence of usual serum markers, but our results are also consistent with the involvement of an unidentified non-A, non-B, non-C agent.

Adult↗
PubMed1993

Basket cells or shadow cells of Gumprecht: a scanning electron microscope study, and the correlation between percentages of basket cells, and cells with altered chromatin structure (dense cells), in chronic lymphocytic leukemia.

For over 50 years the received wisdom has been that the shadow cells of Gumprecht otherwise known as basket cells (BC) are in artefact, produced during preparation of films when a drop of blood is spread on a slide. The assumption has been that they are therefore of no significance. They are commonly seen in blood films from patients with lymphoproliferative syndromes and particularly in chronic lymphocytic leukemia (CLL). In 96 patients with CLL a statistically significant correlation existed between the basket cells observed in films and the lymphocytes with dense chromatin (DC) determined by flow-cytometry. There was no statistically significant correlation between the number of BC and DC, and the anatomic-clinical stage of the disease.

Chromatin↗
PubMed1992

[Allergy to cockroaches in a Swiss population with asthma and chronic rhinitis].

Cockroach extracts are known to contain powerful allergens. In some parts of the world the majority of asthmatics have been shown to be allergic to cockroaches. We have evaluated the prevalence of sensitization to the cockroaches Blattella germanica and Trogoderma angustum in a Swiss population with chronic, non-seasonal asthma and rhinitis. The sera of 110 patients were screened for specific IgE by the RAST technique. We found 10 positive RAST (class 1 to 2). 7 of the 110 patients were sensitized to cockroaches (6.3%). 3 patients had positive RASTs for both species of cockroach. 2 patients had no other detectable allergy (= 5% of those who were considered as non-allergic before the study). These results suggest that allergy to cockroaches is uncommon in Switzerland but can sometimes be detected. We conclude that in Switzerland, screening for hypersensitivity to cockroaches should not be included in routine allergic investigations.

Adolescent↗
PubMed1991

Ceftriaxone plus amikacin in neutropenic patients: a report on 100 cases.

100 febrile patients with chemotherapy-induced neutropenia (less than 0.5 x 10(9)/l) were empirically treated by ceftriaxone (2 g daily in adults, 50 mg/kg daily in children, as a once daily injection) and amikacin (15-20 mg/kg daily). The mean age was 41 years (range 8-72). 51 patients had acute leukemia, 29 non-Hodgkin's lymphoma, 12 Hodgkin's disease, 8 other disorders. 23 febrile episodes were bacteriologically documented (gram-positive: 13 patients; gram-negative: 8 patients; Candida: 2 patients) including 13 cases of bacteremia; 10 were clinically documented, and 67 remained of undetermined origin. Apyrexia was obtained in 39 patients by ceftriaxone plus amikacin alone (success), in 36 patients after the addition of vancomycin and/or amphotericin B (improvement), whereas in the remaining 25 patients it was necessary to substitute the study drug. The failure rate was correlated to the duration of neutropenia: 0/13 when neutropenia less than 6 days; 3/41 (7%) when 6-10 days; 22/46 (48%) when greater than 10 days. Only 2/20 (10%) of patients with neutropenia greater than 20 days were treated with ceftriaxone plus amikacin alone. 9 of the 23 bacteriologically documented episodes were successes (including 6 of the 11 cases due to Staphylococcus), 7 were improvements and 7 were failures (including the 3 cases due to Pseudomonas). No side effects were seen. Ceftriaxone plus amikacin is an effective firstline antibiotic combination in the treatment of febrile neutropenic patients.

Acute Disease↗
PubMed1991

Characterization of normal human bone marrow by flow cytometry.

Fifteen bone marrow samples were obtained from consenting donors for allogenic bone marrow transplantation and were studied by flow cytometry. The simultaneous analysis, cell by cell, of size (forward angle light scattering), structure (right angle light scattering) and surface antigenic expression with 20 monoclonal antibodies allowed selection of ten reproducible cell subsets which were sorted and studied by microscopic examination in order to confirm their distinct characteristics. This very accurate analysis of a bone marrow cytogram should find applications in view of a better characterization of normal and pathological human bone marrow.

Adult↗
PubMed1990

Proliferation of early human myeloid precursors induced by interleukin-1 and recombinant soluble CD23.

Low affinity Fc epsilon receptors (Fc epsilon RII/CD23) or their soluble fragments have various biologic effects on B- and T-cell lineages. In this study, we have assessed the effect of recombinant soluble CD23 (rsCD23) on the proliferation of human bone marrow (BM)-derived myeloid precursors with or without recombinant interleukin-1 (rIL-1) addition. Non-adherent CD2- or CD34+ BM cell subsets were used as target cells. Our results show that rsCD23 in synergy with rIL-1 displays an interleukin-3-like activity as it promotes the proliferation of multipotential marrow precursors. This effect was abolished by anti-CD23 addition to these cultures, but was not affected by anti-IL-3 monoclonal antibody. Furthermore, sequential study indicates that rIL-1 induces bone marrow cell responsiveness to rsCD23.

Antigens, Differentiation, B-Lymphocyte↗