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F Rousset

Publications and source records attributed to F Rousset.

At least 73 records · Page 4Linked to original sources
PubMed1994

High levels of circulating IL-10 in human malaria.

IL-10 is a monocyte/lymphocyte derived cytokine which has been shown to inhibit certain cellular immune responses such as delayed hypersensitivity. In particular, the production of tumour necrosis factor (TNF), IL-1 and IL-6, which are involved in malaria pathology, are strongly inhibited by IL-10. Accordingly, we examined whether IL-10 could be involved in a human acute parasitic infection such as Plasmodium falciparum malaria. Human IL-10 levels in plasma were determined by two-site ELISA method, taking care to avoid non-specific reactions due to autoantibodies. Fourteen cerebral, 11 severe, and 20 mild malaria cases had mean IL-10 levels of 2812, 2882 and 913 pg/ml, respectively, while 98% of healthy individuals had undetectable (less than 100 pg/ml) circulating IL-10. Thirteen of the 25 cerebral/severe cases had > 2000 pg/ml. In 11 hospitalized patients, circulating IL-10 levels were found to return to virtually normal levels 7 days after antimalarial chemotherapy when biological and clinical malaria features had disappeared (mean levels fell from 3880 to 333 pg/ml). Further studies are required to determine whether these elevated levels of IL-10 play a beneficial role by reducing the parasite-induced inflammatory response, or a detrimental one by decreasing the cellular immune responses.

Adolescent↗
PubMed1994

The CD40 antigen and its ligand.

CD40 is an integral membrane protein found on the surface of B lymphocytes, dendritic cells, follicular dendritic cells, hematopoietic progenitor cells, epithelial cells, and carcinomas. It is a 45-50 kDa glycoprotein of 277 aa, which is a member of the tumor necrosis factor receptor superfamily. The CD40 gene maps to human chromosome 20q11-2-q13-2. CD40 binds to a ligand (CD40-L) which is an approximately 35 kDa glycoprotein of 261 aa, a member of the tumor necrosis factor superfamily. The CD40-L gene maps to human chromosome Xq24. This CD40-L is expressed on activated T cells, mostly CD4+ but also some CD8+ as well as basophils/mast cells. The CD40-L is defective in the X-linked hyper-IgM syndrome. Cross-linking of CD40 with immobilized anti-CD40 or cells expressing CD40-L induces B cells to proliferate strongly, and addition of IL-4 or IL-13 allows the generation of factor-dependent long-term normal human B cell lines and the secretion of IgE following isotype switching. Addition of IL-10 results in very high immunoglobulin production with limited cell proliferation. IL-10 induces naive B cells to produce IgG3, IgG1, and IgA1, and further addition of TGF beta permits the secretion of IgA2. Several evidences suggest that CD40-dependent activation of B cells is important for the generation of memory B cells within the germinal centers: (i) CD40 activated germinal center B cells cultured in the presence of IL-4 acquire a memory B cell phenotype, (ii) CD40 activated B cells can undergo isotype switching, (iii) the deficit of CD40-L results in the hyper-IgM syndrome characterized by lack of germinal centers in secondary lymphoid organ follicles and lack of IgG, IgA, and IgE, and (iv) CD40-L positive T cells are present in secondary follicles. Thymic epithelial cells, activated monocytes, and dendritic cells express CD40 antigen which may be involved in an enhanced cytokine production by these cells, allowing an amplification of T cell proliferation. Finally, as other members of the tumor necrosis factor receptor family have been shown to bind several ligands, it is possible that CD40 may bind other ligands that may trigger CD40 on different cell types such as hematopoietic cells or epithelial cells.

Amino Acid Sequence↗
PubMed1994

Human interleukin 4.

Human IL-4 is a mature glycoprotein of 129 amino acids, mostly secreted by activated T cells. It is a pleiotropic cytokine which acts on T and B lymphocytes, monocytes, polymorphonuclears, fibroblasts and endothelial cells. In addition, it acts at various stages of cell differentiation, and its effects are also dependent on the cytokine environment. In particular, IL-4 blocks some of the effects of IL-2 whereas interferon-gamma blocks some of the effects of IL-4. In vitro and in vivo experiments in mouse and in vitro experiments in man have shown that IL-4 plays a crucial role in the induction of IgE production whereas interferons counteract this effect. Human IL-4 binds to a high-affinity receptor which is composed at least of one 130 kDa glycoprotein of 800 amino acids which is a member of the newly described hematopoietin receptor superfamily. IL-4 may prove useful as an anti-tumoral and anti-inflammatory agent.

B-Lymphocytes↗
PubMed1993

Serum interleukin-10 in non-Hodgkin's lymphoma: a prognostic factor.

Serum interleukin-10 (IL-10) was measured retrospectively in 153 patients with a fully documented history of non-Hodgkin's lymphoma (NHL) using an enzyme-linked immunosorbent assay (ELISA) detecting both human IL-10 and the Epstein-Barr virus (EBV) molecule BCRF1/viral IL-10. IL-10 was detectable in 47 (46%) of the 101 patients with active NHL, 3 of 52 (6%) patients in first partial or complete response, and none of the 60 healthy blood donors. Serum IL-10 was detectable with a similar frequency in all subtypes of NHL and in all clinical stages, as well as in EBV-seropositive and EBV-negative patients. In patients with intermediate or high-grade NHL, the presence of detectable serum IL-10 at diagnosis was correlated to a significantly shorter overall (P = .025) and progression-free (P = .030) survival. Patients with stage IV disease and detectable serum IL-10 had a particularly poor prognosis (4 years of survival: 0%). Multivariate analysis showed that IL-10 was an independent prognosis factor. These results indicate that IL-10 is detectable in a subgroup of patients with active NHL and correlates to a poor survival in patients with intermediate or high-grade NHL.

Adolescent↗
PubMed1993

Epstein-Barr virus transformation induces B lymphocytes to produce human interleukin 10.

Interleukin 10 (IL-10) is a pleiotropic factor that enhances proliferation of activated human B lymphocytes and induces them to secrete high amounts of immunoglobulins. Here we show that several human B cell lines were able to constitutively secrete human (h)IL-10. Whereas none of the pre-B nor the plasmocytic cell lines tested produced hIL-10, 25 of the 36 tested mature B cell lines (lymphoblastoid and Burkitt lymphoma cell lines) secreted hIL-10. Moreover, 24 of these 25 hIL-10-producing B cell lines contained the Epstein-Barr virus (EBV) genome, suggesting a relationship between hIL-10 production by human B cell lines and EBV expression. Accordingly, whereas polyclonal activation via triggering of surface immunoglobulins or CD40 antigen induced highly purified normal human B lymphocytes to produce only low (0.3-0.4 ng/ml) but significant amounts of hIL-10, EBV infection induced them to secrete high amounts of hIL-10 (4-9 ng/ml). Furthermore, addition of exogenous hIL-10, simultaneously to EBV infection, potentiated cell proliferation, whereas a blocking anti-IL-10 antiserum inhibited it. Thus, hIL-10 produced by infected human B lymphocytes appears to be involved in the mechanisms of EBV-induced B cell proliferation.

B-Lymphocytes↗
PubMed1993

Induction by anti-CD40 antibody or soluble CD40 ligand and cytokines of IgG, IgA and IgE production by B cells from patients with X-linked hyper IgM syndrome.

We studied the ability of B lymphocytes from patients with X-linked hyper IgM syndrome (HIGM1) to be activated via the CD40 membrane receptor. HIGM1 is caused by a CD40 ligand gene mutation, leading to defective expression on the membrane of activated T lymphocytes. We found that triggering of B cells by an anti-CD40 monoclonal antibody or the soluble CD40 ligand plus interleukin (IL)-4 or IL-10 led to B cell proliferation and/or differentiation towards IgG, IgA and IgE secretion. This was reflected by transcription of C gamma, alpha and epsilon membrane isotype expression and IgG, IgA and IgE production. These results confirm the integrity of B cells in patients with the HIGM1 immunodeficiency and open up new therapeutic possibilities.

Antibodies, Monoclonal↗
PubMed1993

The reproductive incompatibility system in Drosophila simulans: DAPI-staining analysis of the Wolbachia symbionts in sperm cysts.

Any hitherto available technique used to detect the presence of Wolbachia, a rickettsia-like endosymbiont of Drosophila simulans, i.e., crossing with tester strains, electron microscope observations, DAPI-staining of embryo, or amplification of specific sequences by PCR are notably time-consuming techniques. Staining sperm cysts with the fluorochrome DAPI is here shown to be a fast and reliable technique to detect the symbiont and evaluate the level of infection of individual males. Wolbachia cells are abundant in sperm cysts and make up a mass which is eliminated in the waste bag during spermatogenesis. Such a mass was absent in all those strains known to be aposymbiotic. In infected strains, tetracycline treatment led to the disappearance of the symbionts within sperm cysts. In aging males, a decrease in the proportion of infected cysts were observed. There was however no apparent change in the number of symbionts in the cysts which remained infected. The reduction of reproductive incompatibility, which is observed in older males, may be explained by this process, i.e., a decrease in the frequency of infected cysts.

Aging↗
PubMed1993

Role of cytokines in human B lymphocyte growth and differentiation.

B lymphocytes express at their surface the CD40 antigen which belongs to the NGF receptor superfamily. The crosslinking of the CD40 antigen using a mouse fibroblastic cell line expressing the human Fc receptor (Fc gamma RII/CDw32) and anti-CD40 monoclonal antibody induces resting B lymphocytes to enter a state of sustained proliferation. Addition of IL-4 to such cultures results in the generation of factor dependent long-term normal human B cell lines and in the secretion of IgE following isotype switching. Addition of IL-10 results in limited cell proliferation but most importantly in very high immunoglobulin production which results from the differentiation of B cells into plasma cells. The combination of IL-10 and TGF beta induces naive sIgD+ sIgM+ B cells to secrete IgA1 and IgA2 as a consequence of isotype switching. The extracellular domain of CD40 binds with high affinity and high specificity to a 32 kDa glycoprotein transiently expressed on activated T cells. This interaction of the CD40 antigen on B cells with its ligand on T cells represents a key step in T cell dependent B cell activation.

Animals↗
PubMed1993

IL-10 and IL-13 as B cell growth and differentiation factors.

B lymphocytes express at their surface the CD40 antigen which belongs to the NGF receptor superfamily. The crosslinking of the CD40 antigen using a mouse fibroblastic cell line expressing the human Fc receptor (Fc gamma RII/CDw32) and anti-CD40 monoclonal antibody induces resting B lymphocytes to enter a state of sustained proliferation. Addition of IL-4 or IL-13 result in the proliferation of human B cells and in the secretion of IgE following isotype switching. Addition of IL-10 permits limited cell proliferation but most importantly results in very high immunoglobulin production following differentiation of B cells into plasma cells. In response to IL-10, unseparated B cells cultured in the CD40 system produced the four IgG subclasses in ratio comparable to those observed in the serum. IL-10 induces naive B cells to secrete low but reproducible amounts of IgG and IgA. The combination of IL-10 and TGF beta induces naive B cells to secrete IgA1 and IgA2 as a consequence of isotype switching. The extracellular domain of CD40 binds with high affinity and high specificity to a ligand transiently expressed on activated T cells. This interaction of the CD40 antigen on B cells with its counter-structure on T cells represents a key step in T cell dependent B cell activation.

Antigens, CD↗
PubMed1992

Wolbachia endosymbionts responsible for various alterations of sexuality in arthropods.

Rickettsia-like maternally inherited bacteria have been shown to be involved in a variety of alterations of arthropod sexuality, such as female-biased sex ratios, parthenogenesis, and sterility of crosses either between infected males and uninfected females or between infected individuals (cytoplasmic incompatibility). We have characterized several of these microorganisms through partial sequences of the small (16S) and large (23S) subunit ribosomal DNA. All the symbionts identified, which include several cytoplasmic incompatibility microorganisms, several endosymbionts of terrestrial isopods, and symbionts of two thelytokous Trichogramma wasp species, belong to a monophyletic group of related symbionts, some of which have previously been detected in several insects exhibiting cytoplasmic incompatibility. Three molecular lineages can be identified on the basis of 16S as well as 23S sequences. Although they are only known as endocellular symbionts, Wolbachia spread by horizontal transfer across host lineages as evidenced by their diversification which occurred long after that of their hosts, and by the non-congruence of the phylogenetic relationships of symbionts and their hosts. Indeed, symbionts of two different lineages have been found in the same host species, whereas closely related endosymbionts are found in distinct insect orders. Isopod endosymbionts form a separate lineage, and they can determine feminization as well as cytoplasmic incompatibility. The ability to determine cytoplasmic incompatibility, found in all lineages, is probably ancestral to this group.

Animals↗
PubMed1992

Molecular identification of Wolbachia, the agent of cytoplasmic incompatibility in Drosophila simulans, and variability in relation with host mitochondrial types.

Sequences of a segment of the 16S ribosomal DNA of Wolbachia, a rickettsia-like microorganism responsible for cytoplasmic incompatibility in Drosophila simulans, have been obtained after polymerase chain reaction (PCR) amplification. Their comparison with other eubacterial sequences allows us to assign these endosymbionts to the alpha subdivision of purple bacteria. Four related sequences have been obtained for microorganisms carried by eight isofemale lines representative of the three mitochondrial types of D. simulans. Their phylogeny and level of divergence do not parallel that of the mitochondrial DNA, suggesting that several independent infections occurred. There is no direct relation between bacterial phylogeny and formerly identified incompatibility types.

Animals↗
PubMed1992

Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes.

Interleukin 10 (IL-10), originally identified as a TH2 helper T-cell product able to inhibit cytokine production by TH1 cells, is highly homologous to BCRF1 (viral IL-10), an open reading frame in the Epstein-Barr virus genome. Here, we show that human and viral IL-10 stimulate DNA replication of B lymphocytes activated either via their antigen receptor or via their CD40 antigen. IL-4 and IL-10 display additive effects and induce a strong increase in the number of viable cells. Moreover, IL-10 induces activated B cells to secrete large amounts of IgG, IgA, and IgM, and the combination of IL-10 and IL-4 results in the secretion of the four immunoglobulin isotypes. Thus, IL-10 may play an important role in the amplification of humoral responses.

Antibody Formation↗
PubMed1992

Interleukin 10 and transforming growth factor beta cooperate to induce anti-CD40-activated naive human B cells to secrete immunoglobulin A.

In the present report, we have investigated the in vitro differentiation of surface(s) sIgD+ and sIgD- human B cells into Ig-secreting cells in response to various stimuli. sIgD+ B cells homogeneously expressed some of the antigens identifying mantle zone B cells, but lacked expression of germinal center markers, thus confirming that the B cell populations positively selected on the basis of sIgD expression were highly enriched for naive B lymphocytes. Conversely, sIgD- B cells expressed some of the antigens specifically associated with germinal center B cells. T cell-independent differentiation of sIgD+ and sIgD- B cells could be achieved by simultaneous crosslinking of sIgs and CD40 in the presence of a mouse Ltk- cell line stably expressing human CDw32/Fc gamma RII (CDw32 L cells). In this experimental system, sIgD+ B cells were exclusively proned for IgM synthesis, whereas sIgD- B cells produced IgG, IgM, and IgA. Both the human and viral forms of interleukin 10 (IL-10) strongly increased the Ig secretion by sIgD+ and sIgD- B cells simultaneously activated through sIgs and CD40. IgM and IgG constituted the predominant Ig isotype produced by sIgD+ and sIgD- B cells, respectively, in response to IL-10. sIgD+ B cells could be induced for IgA synthesis upon co-culturing with transforming growth factor beta (TGF-beta) and IL-10, in the presence of an anti-CD40 monoclonal antibody presented by the CDw32 L cells. In contrast, TGF-beta suppressed the IL-10-mediated IgG, IgM, and IgA secretions by sIgD- B cells. sIgD+ B cells could not be induced for IgA synthesis by TGF-beta and IL-10 after crosslinking of their sIgs, suggesting that ligation of CD40 was one of the obligatory signals required for commitment of naive B cells to IgA secretion. Limiting dilution experiments indicated that the IgA-potentiating effect of TGF-beta was due to its capacity to increase the frequency of IgA-producing cells, most likely as a consequence of class switching. Taken together, our data strongly suggest that TGF-beta is involved in the regulation of IgA isotype selection in humans.

Antibody-Producing Cells↗
PubMed1991

Evolution of compensatory substitutions through G.U intermediate state in Drosophila rRNA.

It has often been suggested that the frequently observed Watson-Crick base-pair compensatory substitutions in RNA helical structures occur mainly through a slightly deleterious G.U intermediate state. We have scored base substitutions in a set of 82 related Drosophila species for the D1 and D2 variable domains of the large rRNA subunit. In all locations where a G-C in equilibrium with A-U compensatory base change occurred, a G.U pair has been observed in one or several species. As this dominant process implies two transitions, their rate was far higher in paired regions (92%) than in unpaired regions (47%). The other types of compensation were rarer and no intermediate states were observed. Most of the G.U base pairs observed in a species are not slightly deleterious. The rate of evolution of compensatory substitution is close to that predicted by a simple model of compensatory substitution through slightly deleterious or slightly advantageous G.U pairs, although some exceptions are presented.

Animals↗
PubMed1991

Growing human B lymphocytes in the CD40 system.

One approach to generating human monoclonal antibodies relies on the development of culture techniques allowing the long-term growth of most B lymphocytes, a property of the CD40 system.

Antibodies, Monoclonal↗
PubMed1991

Cytokine-induced proliferation and immunoglobulin production of human B lymphocytes triggered through their CD40 antigen.

Human resting B lymphocytes enter a state of sustained proliferation when incubated with both mouse fibroblastic L cells stably expressing Fc gamma RII/CDw32 and anti-CD40 antibodies. We have explored the effects of 11 recombinant human cytokines (CKs) on induced cell proliferation and immunoglobulin (Ig) production. Interleukin 4 (IL-4) was the only CK able to enhance anti-CD40-induced B cell multiplication as measured by enumeration of viable cells, and interferon gamma (IFN-gamma) further stimulated this induced proliferation. IL-4 enhanced the production of IgM and IgG by B cells and induced them to produce IgE. Combinations of IL-4 and IL-2 resulted in the production of large amounts of IgM and IgA. Interestingly, IFN-gamma did not inhibit the production of IgE by cells stimulated with anti-CD40 and IL-4. None of the tested CK combinations resulted in the production of large quantities of IgG. Therefore, this new culture system represents a unique model to study isotype regulation in highly purified human B lymphocytes, in addition to allowing the generation of long-term factor-dependent human B cell lines.

Antibodies, Monoclonal↗
PubMed1991

Long-term human B cell lines dependent on interleukin-4 and antibody to CD40.

CD40 is a 45- to 50-kilodalton transmembrane glycoprotein expressed on B lymphocytes, epithelial cells, and some carcinoma cell lines. Human resting B lymphocytes entered a state of sustained proliferation when incubated with both the mouse fibroblastic Ltk- cell line that had been transfected with the human Fc receptor (Fc gamma RII/CDw32) and monoclonal antibodies to CD40. In combination with interleukin-4, factor-dependent long-term normal human B cell lines were generated that were consistently negative for Epstein-Barr viral infection. Thus, cross-linking of CD40 is likely to represent an important phenomenon in the clonal expansion of B cells.

Antibodies, Monoclonal↗