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M Seman

Publications and source records attributed to M Seman.

At least 55 records · Page 3Linked to original sources
PubMed1993

Rearrangement by chromosomal inversion in the T cell receptor gamma locus in a murine alpha beta T cell clone.

Analyzing the T-cell receptor (TCR) repertoire of T lymphocytes specific for minor histocompatibility antigens, we isolated a TCR-alpha beta bearing T cell clone, TGVH9, which also expresses three different TCR-gamma mRNA. The sequences of these messengers indicate that one of them results from the rearrangement of V gamma 1 and J gamma 2 genes. Since these two segments are in inverted genomic transcriptional orientation, the joining of V gamma 1 to J gamma 2 occurred by chromosomal inversion. This mechanism, which was previously reported in TCR-beta and TCR-delta loci, can thus also occur to enlarge the diversity of the TCR-gamma repertoire.

Amino Acid Sequence↗
PubMed1993

Preferential V delta 1 expression among TcR gamma/delta-bearing T cells in human oral epithelium.

The oral cavity is a septic area colonized by various bacterial species, and the oral mucosa is frequently submitted to microtraumas. Several mechanisms are implicated in the defence of the oral tissue, but little is known concerning the eventual presence and role of gamma/delta T cells at this site. Samples of healthy keratinized oral mucosa were examined with immunochemical techniques using anti-CD3, CD4, CD8, CD22, TcR delta 1, V delta 1 and V delta 2 monoclonal antibodies. Whatever the site examined, gamma/delta T cells represent at most 2% of the T-cell population, a value similar to that found in other tissues. In the connective tissue, under the basement membrane, V delta 2+ gamma/delta T cells are predominant whereas the epithelium mostly contains V delta 1+ gamma/delta T cells. The significance of this preferential V delta 1 intraepithelial presence is discussed.

B-Lymphocytes↗
PubMed1993

Mls-1 and Mls-2 superantigens do not control susceptibility to collagen-induced arthritis in HI and HII mice.

The HI mouse line is sensitive to collagen-induced arthritis (CIA), whereas HII is refractory, although both express the H-2q permissive haplotype. The two lines also share the same T-cell receptor (TcR) gene haplotypes for alpha and beta chains. The distribution of mouse mammary tumour viruses (MMTV), which encode endogenous superantigens (SAg) such as minor leucocyte-stimulating antigens (Mls) known to modulate the available TcR-V beta repertoire, was investigated in the two lines. Mls-1 is present in HI-susceptible mice, while Mls-2 and Mls-2-like SAg are absent in both lines. This suggests that Mls antigens play no significant role in the resistance to CIA. Moreover, HI and HII exhibit close V beta gene usage as assessed by fluorescence staining with 11 V beta-specific monoclonal antibodies (mAb). These results indicate that mechanisms other than clonal deletion based on V beta expression and induced by SAg are involved in the resistance of H-2q-positive mice to experimental arthritis. Yet, a slightly reduced level of V beta 5+ T cells is observed in HII animals which might correlate with the presence of Mtv-6 and Mtv-9 proviruses.

Animals↗
PubMed1992

Activity of MS-8209, a nonester amphotericin B derivative, in treatment of experimental systemic mycoses.

The in vitro and in vivo toxicities and activities of MS-8209, a new hydrosoluble amphotericin B (deoxycholate-amphotericin B [D-AmB]; Fungizone) derivative, were studied. In vitro, MS-8209 was less toxic than AmB against renal tubular cells in primary culture and less active against Candida albicans and Cryptococcus neoformans. However, at 10-fold the AmB concentration, MS-8209 in vitro antifungal activity paralleled that of AmB. Fifty-percent lethal doses of MS-8209 and D-AmB in OF1 noninfected mice were 26 and 2.3 mg/kg, respectively. Therapeutic efficacy of MS-8209 was assessed in murine candidiasis, cryptococcosis, and aspergillosis. In each model of infection, we determined the maximum tolerated dosages of MS-8209 and D-AmB, i.e., the dosage inducing less than 15% mortality due to toxicity; the efficacies of MS-8209 and D-AmB at their respective maximum tolerated dosages were compared. In candidiasis, MS-8209 (15 mg/kg) significantly increased the survival time compared with D-AmB (0.5 mg/kg). Both compounds were equally effective at reducing CFU counts in the kidney. MS-8209 was the most effective agent for increasing the survival time in cryptococcal meningoencephalitis and for reducing CFU counts in spleen, brain, and lung during both cryptococcal pneumonia and meningoencephalitis. In aspergillosis, MS-8209 and D-AmB similarly prolonged the survival of treated mice compared with controls. These results show that when MS-8209 and D-AmB were used at the maximum tolerated dosage, MS-8209 was as effective as or more effective than D-AmB for the treatment of systemic mycoses. These findings warrant further experiments to study the pharmacokinetic properties and toxicity of MS-8209 under conditions of chronic administration.

Amphotericin B↗
PubMed1991

Resistance to collagen-induced arthritis in Biozzi mice is not associated with T cell receptor V beta gene polymorphism.

H-I and H-II high antibody-responder Biozzi mice, which express the H-2q permissive haplotype, were shown to be sensitive and refractory to collagen-induced arthritis, respectively. To assess a possible role of T cell receptor (TcR) V beta gene deletion or polymorphism in the resistance to arthritis in H-II mice, the germinal structure of TcR V beta genes and their expression at the membrane level were compared in both lines. In contrast to H-2q refractory SWR mice, which exhibit a deletion of about 50% of TcR V beta gene segments. H-I and H-II lines have an identical and complete set of V beta genes and exhibit no difference in the average expression of V beta 6, V beta 8 and V beta 11 gene products on T cell surface. These results indicate that mechanisms other than V beta gene deletion or polymorphism can be involved in the resistance of H-2q-positive mice to experimental arthritis.

Animals↗
PubMed1991

MS-8209, a new Amphotericin B derivative that inhibits HIV-1 replication in vitro and restores T-cell activation via the CD3/TcR in HIV-infected CD4+ cells.

A new Amphotericin B derivative, MS-8209, which retains high antifungal activity with greatly reduced toxicity and improved solubility, has been developed. We investigated the antiviral properties of MS-8209 in Jurkat and CEM T-cell lines and in peripheral blood mononuclear cells infected in vitro with HIV-1BRU. Our results demonstrate, by determination of reverse transcriptase activity and p24 antigen level titration in cell culture supernatants, that MS-8209 inhibits HIV-1 replication in all cell types at concentrations without cytotoxicity. MS-8209 also prevents membrane expression of the HIV-1 large envelope glycoprotein gp120 and the decrease in CD4 level at the surface of infected cells. HIV-1-infected Jurkat cells exhibit a severe signalling defect at CD3 stimulation. Treatment with MS-8209 restores normal responsiveness at CD3 as assessed by measurement of inositol triphosphate accumulation and calcium flux. Finally, our results indicate that MS-8209 inhibits HIV-1BRU replication without preventing virus binding and penetration into target cells.

Amphotericin B↗
PubMed1990

Autoreactive T cells in normal mice: unrestricted recognition of self peptides on dendritic cell I-A molecules by CD4-CD8- T cell receptor alpha/beta+ T cell clones expressing V beta 8.1 gene segments.

CD4-CD8- double-negative (DN) and CD4+CD8- T cell clones were derived from splenic precursors resistant to killing by anti-Thy-1, -CD5, -CD4 and -CD8 monoclonal antibodies and complement. Both DN and CD4+ clones express functional T cell receptor (TcR) alpha/beta and exhibit strong autoreactivity in vitro. DN cells can be induced to proliferate by dendritic cells (DC) of all haplotypes tested, although this activation is inhibited by antibodies specific for I-A determinants expressed on the stimulatory DC. In contrast, CD4+ clones only respond to syngeneic or I-Ad-compatible DC. Both DN and CD4+ autoreactive clones do not proliferate when cultured with class II+ H-2d normal or tumor macrophages and B cell lines or with class II-transfected L cells, suggesting that these cells recognize self peptides only present on the surface of DC. Despite their phenotype resembling that of immature thymocytes and their inability to interact directly with B lymphocytes, DN cloned T cells, like CD4+ T cells, exhibit nonspecific helper functions and can induce polyclonal B cell proliferation and differentiation. DN TcR alpha/beta+ peripheral T cells represent, like TcR gamma/delta+ lymphocytes, a new T cell subset physiological role whose remains to be defined.

Animals↗
PubMed1990

Polymorphism of Tcrb and Tcrg genes in Biozzi mice: segregation analysis of a new Tcrg haplotype with antibody responsiveness.

Tcrb and Tcrg gene polymorphism was investigated in high (H) and low (L) responder Biozzi mice from selection I, II, and GS by Southern blot analysis with appropriate V and C probes. No polymorphism of the Tcrb haplotype was detected between H and L mice in all selections which were all found to be of the BALB/c type. The H-I and H-II g genotype was of BALB/c and DBA/2 type, respectively. In contrast, a new Tcrg haplotype shared by L-I and L-II mice was identified and characterized by C gamma 1, 2, 3, C gamma 4, V gamma 1, 2, 3, V gamma 5, and V gamma 6 restriction fragment length polymorphisms (RFLPs). Tcrg genotypes were not fixed in the GS selection and two additional new haplotypes were identified in two L-GS mice. An attempt was made to correlate the L-I g genotype with the low responder status by analyzing g haplotypes among highest and lowest responder (H-I X L-I)F2 hybrids immunized with sheep red blood cells (SRBC). No correlation was found in this segregation study, whereas a highly significant one was established with the H-2 haplotype, a locus already known to participate in the genetic control of H-I/L-I difference. The lack of correlation between SRBC response and the Tcrg genotype was consistent with the heterogenous g haplotypes found in mice of the GS selection. Together, the present results suggest that H and L mice have the same Tcrab potential repertoire and that T-cell receptor (Tcr) genes cannot be considered as immune response genes in this model. Our results also indicate that the F2 segregation analysis, given a polymorphic gene, is suitable for an investigation of its immune response functions.

Animals↗
PubMed1990

Induction of interleukin-3 by interleukin-1 in the absence of other exogenous stimuli.

We have previously reported that lipopolysaccharide (LPS) could induce the production of interleukin-3 (IL-3) by mouse spleen cells. In the present study, we show that recombinant human interleukin-1, in the absence of other stimuli, is able to induce the production of IL-3. IL-3 was detected in the supernatants of adult, although neither in young nor in nude mouse splenocytes and was assessed by its capacity to support the growth of the IL-3-dependent FDC-P2 cell line. The presence of IL-3 was antigenically confirmed with a monoclonal anti-IL-3 antibody. Both recombinant IL-1 alpha and IL-1 beta had similar potential for inducing IL-3 production. IL-3 activity was detected in the supernatants of cells cultured in the presence of 100 pg/ml IL-1; maximal IL-3 levels were obtained with 10-30 ng/ml IL-1. Kinetic studies of IL-1-induced IL-3 production indicated that 4-6 days of culture were required for optimal production, whereas 1-2 days were sufficient in cultures stimulated with concanavalin A. Recombinant IL-6 failed to induce significant amounts of IL-3, and TNF alpha induced only weak IL-3 production. GM-CSF but not M-CSF could lead to the appearance of IL-3 in spleen cell culture supernatants. Removal of macrophages decreased the production of IL-3 induced by LPS and GMF-CSF though did not affect the IL-3 production induced by IL-1. This observation suggests that IL-1 production might be an intermediate event in IL-3 production induced by LPS and GM-CSF through the activation of macrophages. IL-3 was detected in culture supernatants of B-cell-depleted splenocytes indicating that T-cells were the source of IL-3. Surprisingly T-cell-depleted populations could also produce IL-3 upon IL-1 stimulation. Preliminary experiments with an autoreactive CD4- CD8- V beta 8+ clone suggested that these cells might also be involved in the described IL-3 production.

Animals↗
PubMed1990

Induction of mouse syngeneic MLR by in vivo xenogeneic immunization with HLA-DR antigens.

To study in mice the effects of in vivo xenogenic immunization with human major histocompatibility complex (MHC) class II antigens, the animals were injected with HLA-DR antigens and their proliferative responses tested in vitro. The results showed that small amounts of HLA-DR proteins, acting as nominal antigens, were not only able to prime mice for a secondary in vitro xenogenic mixed lymphocyte reaction but also induced a syngeneic mixed lymphocyte reaction. In contrast, allogeneic or syngeneic immunization of mice with soluble MHC class II molecules failed to stimulate an autoreactive response. The syngeneic mixed lymphocyte reaction was primarily directed against syngeneic MHC class II molecules since the murine T lymphocytes reacted against MHC class II-positive dendritic spleen cells and MHC class II-transfected mouse fibroblasts. A self-reactive T-cell line induced under these experimental conditions did not react in xenogeneic and allogeneic mixed lymphocyte reactions. However, these T lymphocytes proliferated when human peripheral blood lymphocytes of various haplotypes were presented in the context of syngeneic mouse antigen presenting cells.

Animals↗
PubMed1989

Interaction of amphotericin B and its N-fructosyl derivative with murine thymocytes: a comparative study using fluorescent membrane probes.

The polyene antibiotics amphotericin B (AmB) and N-(1-deoxy-D-fructos-1-yl)amphotericin (N-Fru-AmB) have different activity towards murine thymocytes (N-Fru-AmB is less toxic but is a potent immunomodulator). The interactions of the drugs with these cells have been studied by fluorescence methods. Fluorescence energy transfer from 1-[4-(trimethylammonio) phenyl]-6-phenylhexa-1,3,5-triene, p-toluenesulfonate (TMA-DPH) to polyenes was used to follow the binding of the two drugs to the plasma membrane. The results, confirmed by circular dichroism measurements, indicate that at saturation the ratio AmB bound/plasma membrane lipid is low (less than 1 molecule of polyene for 170 lipids). The slightly higher binding of AmB as compared to N-Fru-AmB demonstrates that affinity of the antibiotic for plasma membrane does not account for the activity of the polyenes towards lymphocytes. The effect of the two polyenes on membrane fluidity was studied by steady-state fluorescence anisotropy. The results suggest that AmB strongly perturbs the structure of the membrane whereas only a slight decrease of the anisotropy is observed with N-Fru-AmB in the range of concentration where the biological activity has been demonstrated. Polyene location was further investigated by comparing the energy transfer efficiency obtained with TMA-DPH and with the parental compound 1,6-diphenylhexa-1,3,5-triene, p-toluene sulfonate (DPH). While AmB binds to plasma membrane, as well as to intracellular structures, N-Fru-AmB seems to accumulate into the cell and bind to intracellular membrane structures.

Amphotericin B↗
PubMed1989

Immunomodulating properties of the N-(1-deoxy-D-fructos-lyl) derivative of amphotericin B in mice.

Immunomodulating properties of the N-(1-deoxy-D-fructos-lyl) derivative of Amphotericin B (N-Fru-AmB) was investigated in vitro on T and B mouse lymphocytes and compared to that of the original AmB molecule. Results indicate that N-Fru-AmB is a potent polyclonal B cell activator capable of inducing B lymphocytes to proliferate and to differentiate into Ig secreting cells in absence of any additional signal. N-Fru-AmB is also mitogenic for a fraction of peripheral T lymphocytes. Together, the results suggest a potential interest of such derivatives in the treatment of mycosal infections in immunodeficient patients.

Adjuvants, Immunologic↗
PubMed1988

Genetics and strain distribution of concanavalin A-reactive Ly-2-, L3T4- peripheral precursors of autoreactive T cells.

Cytotoxic treatment of BALB/c cells from different peripheral lymphoid tissues by a cocktail of monoclonal antibodies against Thy-1, Ly-1, L3T4 and Ly-2 differentiation markers (anti-T cocktail) plus complement eliminates all mature T lymphocytes. Yet a population of dull Thy-1+, Ly-1-, L3T4-, Ly-2-, corresponding to about 1% of the initial population, can be detected by flow cytometry which proliferate under concanavalin A stimulation. These anti-T killing-resistant cells (TKR) were previously shown to be capable of differentiating in culture into class II-restricted autoreactive T helper cells. We demonstrate here that such cells can be detected in mice of BALB/c and DBA/2 genetic background but are absent in C57BL/6 and B10 animals. The presence of TKR cells is dominant in (BALB/c x C57BL/6)F1 hybrids and genetically controlled by two genes which are neither H-2 nor Igh linked. TKR cells are also detected in young NZB mice but disappear with the development of the systemic autoimmune disease in old animals. Thy-1+, L3T4-, Ly-2- cells from MRL lpr/lpr mice also respond to concanavalin A but are removed by the anti-T treatment. Altogether, arguments are presented suggesting that TKR cells represent a particular subset of double-negative peripheral T cells which may correspond to autoreactive T cell recursors that would escape the thymic selection. We postulate that these cells are present in all mouse strains but their susceptibility to killing by anti-Thy-1 antibodies differs depending on background genes.

Animals↗
PubMed1987

Influence of kappa and IgH genes on the T helper cell response to p-azobenzenearsonate tyrosine.

Immunization of mice with the p-azobenzenearsonate-L-tyrosine conjugate (ABA-Tyr) leads to the activation of ABA-specific T helper cells capable of proliferating in vitro in the presence of the corresponding antigen. This response is under a dual genetic regulation by H-2 and non-H-2 linked genes, and H-2d mice are high-responder. We demonstrate here, using strains congenic to BALB/c for chromosomes (Chr.) 6 or 12 that this T cell response is also influenced by kappa and IgH linked genes. Double congenic mice indicate that Chr.6 and Chr.12 genes have a complementary effect on the response which cannot be predicted solely by the alleles expressed on either of the two chromosomes. In addition, responses in Bailey's inbred recombinant mice allow a possible mapping of the Chr.12 gene at the 5' end of the IgH complex and of the VH-dextran gene family. The mechanisms which may account for the influence of immunoglobulin gene products on the ABA-specific T cell repertoire are discussed.

Animals↗
PubMed1986

Origin of autoreactive T helper cells. I. Characterization of Thy-1+, Lyt-, L3T4- precursors in the spleen of normal mice.

A new population of dull Thy-1+, Ly-1-, Lyt-2-, L3T4- PNA- cells, resistant to a double cytotoxic treatment by monoclonal antibodies to these T cell markers plus complement, has been isolated from the spleen of normal adult BALB/c and DBA/2 mice (Tkr cells). These cells exhibit no spontaneous autoreactivity or alloreactivity but can be activated with concanavalin A (Con A). Once activated, they differentiate into bright Thy-1+, Ly-1+, Lyt-2-, L3T4+ PNA- T lymphocytes. Con A-activated Tkr cells also strongly proliferate in the presence of allogeneic or syngeneic dendritic cells in secondary cultures. Moreover, contrary to other Con A-stimulated T cell populations, they induce B lymphocytes to proliferate and to differentiate into Ig-secreting cells at a very high level. Con A-activated Tkr cells are therefore very potent polyclonal B cell activators. Restimulated of Tkr cells by syngeneic dendritic cells can be inhibited by anti-L3T4 or anti-class II monoclonal antibodies. The results suggest that Tkr cells are the precursors of class II-specific autoreactive T helper cells. Tkr cells are absent in the spleen of B6 animals. This indicates that their expression might be genetically controlled. It also suggests that Tkr cells may not be the unique splenic precursors of autoreactive T cells. Con A activation of Tkr cells in Click's medium is 2-mercaptoethanol dependent and highly sensitive to pCO2, like the response of thymocytes. Tkr cells are also absent in the spleen of nude mice. We conclude that Tkr cells represent splenic precursors of autoreactive T helper cells equivalent to Thy-1+, Ly-2-, L3T4- PNA- cortical thymocytes.

Animals↗
PubMed1985

Epitope-specific regulation of the T cell repertoire: carrier recognition in association with I-E or I-A does not influence the restriction of hapten-specific T cells.

The T cell repertoire of BALB/c mice contains clones capable of recognizing p-azobenzenearsonate (ABA)-tyrosine (Tyr) in association with both I-A and I-E-encoded class II molecules. Immunization of BALB/c animals with ABA-GAT (terpolymer of L-Glu60-L-Ala30-L-Tyr10) or ABA-GLT (terpolymer of L-Glu51-L-Lys34-L-Tyr15) instead of ABA-Tyr reduces the secondary proliferative response to ABA-Tyr in vitro. Limiting dilution experiments indicate that this situation corresponds to the recruitment of fewer ABA-specific T cells in vivo. The same experiments, performed in A.TH mice, which are nonresponder to both GAT and GLT, demonstrate that the number of ABA-specific T cells stimulated in vivo with ABA conjugates depends on the Ir gene-controlled immunogenicity of the carrier rather than on the ABA epitope density on the immunogen. Although GAT is preferentially recognized in association with A, and GLT with E, ABA-GAT and ABA-GLT stimulate both A and E-restricted ABA T cells in vivo and in vitro. The ABA-Tyr-specific T cell repertoire is not qualitatively affected by the carrier. This demonstrates that the inhibition of hapten-specific T cell expression upon immunization with ABA conjugates does not result from a competition between hapten and carrier-specific T cells for epitope recognition in association with the same Ia molecule on antigen-presenting cells.

Animals↗