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Biomedical subjects

D Oth

Publications and source records attributed to D Oth.

At least 37 records · Page 2Linked to original sources
PubMed1989

[Role of liposomes in the presentation of HIV envelope glycoprotein and the immune response in mice].

The role of antigen presentation in the induction of humoral as well as cell-mediated immune responses has been investigated by anchoring HIV-1 envelope glycoprotein (gp 160/120) into the phospholipidic bilayer of preformed liposomes to produce HIV-Immunosomes. HIV-Immunosomes induced high titres of HIV-specific antibodies when tested by ELISA, IFA and neutralization, whereas equal amounts of purified glycoprotein alone produced lower antibody response. Similarly, HIV-Immunosomes induced antigen-specific Interleukin-2 production and blastogenic response upon restimulation with the same antigen, in animals vaccinated with HIV-Immunosomes, whereas no secondary response was observed in animals vaccinated with equal amounts of purified gp 160/120. Taken together, these results underline the importance of antigen presentation in the establishment of an adequate immune status and show the potential of HIV-Immunosomes as vaccine against AIDS.

Animals↗
PubMed1988

Interactions between lymphoid cells and a thymic stromal cell line in vitro.

In the present study, we have optimalized the adherence assay to allow monitoring of the level of contact between thymocytes and a thymic epithelial cell line, E-5, in vitro. This type of interaction is not MHC-restricted, thus is unlikely to participate in the education of thymocytes to self. It was also shown that adherence does not vary from strain to strain, except for B6lpr/lpr immunodeficient mice which showed a markedly decreased adherence. This might be caused by the high level of L3T4-, Lyt-2- thymocytes in these mice (Davignon et al., 1985), since enriched double negative cells were shown not to adhere to E-5 cells. Preliminary characterization of adhering thymocytes suggests an heterogeneous mature phenotype. These cells appear around day 16 of fetal life and increase gradually until birth to remain constant throughout life. On the basis of contact duration, two populations of adhering thymocytes exist: one spontaneously detached after 1.5 hr, refractive to further adherence and the other which adheres for up to 14 hr. Contact between lymphoid and E-5 cells was shown to induce PHA responsiveness.

Animals↗
PubMed1988

Tac expression induced by Epstein-Barr virus is restricted on non-transformable B lymphocytes.

During the course of a comparative study dealing with the immortalization of lymphocytes from a large number of normal healthy donors, we found that B cells of two of these individuals could not be immortalized by Epstein-Barr virus (EBV) under the standard conditions. The expression of the Tac antigen on the membrane of EBV-infected B cells from these two donors was compared with that of B cells from EBV immortalization-susceptible ones. The method used was two-colour immunofluorescence cytofluorometer analysis. We found that the Tac antigen expression was significantly and repeatedly reduced in the case of the two immortalization-resistant donors. This difference might be related to a genetic control of the resistance to EBV-immortalization.

B-Lymphocytes↗
PubMed1988

Enhancement of antigen-specific interleukin 2 production by adding liposomes to rabies antigens for priming.

Antigen-specific IL-2 production was assessed, using splenocytes from rabies immune mice incubated for 24 h with rabies virus antigen. The antigenic material used for in vivo priming was either purified glycoprotein from rabies virus, or the inactivated virus. The time between priming, harvesting and restimulation of the splenocytes was 7 days. It was found that when antigenically inert liposomes were injected, together with antigenic material, to the prospective splenocyte donor mice, IL-2 production was enhanced. This augmentation was observed particularly when priming was performed with the inactivated rabies virus.

Animals↗
PubMed1988

Interleukin-2 production in vitro: a new approach to the study of rabies vaccine immunogenicity as appraised by testing different glycoprotein presentations.

When injected as an immunosome presentation (molecules anchored to preformed liposome), rabies glycoprotein (GP) is capable of protecting animals against rabies either before or after viral infection. The presentation of the GP molecules in the correct form seems to be essential for the induction of antirabies protection. This condition must be taken in account in the making-up of a rabies subunit vaccine. In order to study the relationship between the immune responses induced by the rabies GP and its protective activity, different presentations of the GP were prepared. Purified glycoprotein molecules were associated under different physical forms: liposome-anchored, self-aggregated (rosettes) and associated with the viral lipids (virosomes). These presentations appeared different on electron microscopy. They also exhibited differences in the expression of an immunodominant epitope and in their protective activity. The non-specific immune response, as appraised by interferon production and natural cytotoxicity, was induced at a high level only by the purified viral particles. Specific immune responses (namely virus neutralizing antibody and interleukin-2 production) was induced at high levels only by the viral particle and by the liposome-anchored glycoprotein. A parallelism has previously been established between protection by glycoprotein preparations and interleukin-2 production in primed mice splenocytes. This suggests that the measure of interleukin-2 production in vitro could be used to evaluate the capability of a rabies antigen to induce a T-cell response and to confer protection.

Animals↗
PubMed1988

Interleukin 2 increases protection against experimental rabies.

Vaccination with either whole inactivated rabies virus or immunosome (rabies glycoprotein anchored on liposomes) induces a high level of interleukin 2 (IL 2) production after in vitro specific stimulation of splenocytes from primed mice (9). On the contrary, infection with a live rabies virus does not specifically induce the production of IL 2: splenocytes from ill mice previously infected with wild rabies virus cannot be specifically stimulated by rabies antigens, whereas they can be non-specifically stimulated by a mitogen (Concanavalin A (Con A]. When injected in mice, exogenous IL 2 (purified rat IL 2 or human recombinant IL 2) exhibits an adjuvant effect on rabies virus vaccine or subunit vaccine tested in a pre-exposure potency test (NIH test). When injected in hamsters, according to a post-exposure potency test (infection with a wild rabies virus followed by vaccination), IL 2 has no adjuvant effect on the rabies vaccine. Nevertheless, when injected alone, IL 2 protects thirty to fifty percent of the infected animals treated (1 hour, 3 and 7 days post-infection) with 10 international units of human recombinant IL 2.

Animals↗
PubMed1987

Induction, by adriamycin and mitomycin C, of modifications in lipid composition, size distribution, membrane fluidity and permeability of cultured RDM4 lymphoma cells.

Adriamycin and mitomycin C were previously found to modulate the sensitivity of lymphoma cells to lysis by certain effectors of immunity and this modulation was dependent on drug concentration. In the present studies, RDM4 lymphoma cells were treated with different concentrations of the two drugs for 24 h in culture. These treatments resulted in changes in the lipid composition, membrane fluidity, cell size distribution, and permeability to 51CrO4, Trypan blue, Acridine orange and trimethylaminodiphenylhexatriene (TMA-DPH) of the cells. Changes in some of these parameters, as a function of drug concentration, resulted in dose-response curves which were bell-like shaped, hence paradoxical similarities between non-drug-treated cells and cells treated with higher drug concentrations were observed.

Animals↗
PubMed1987

Protection from mouse hepatitis virus type 3-induced acute disease by an anti-nucleoprotein monoclonal antibody. Brief report.

Fusion of MHV-3-immune splenocytes from MHV-3-resistant A/J murine strain, with NS myeloma cells produced several hybridomas. Among eight hybridoma clones, the 1E7A4H1 clone secreted kappa IgG2a apparently directed against the nucleoprotein of the MHV-3 virion. The monoclonal antibody was able to neutralize the in vitro cytopathic effect of MHV-3 on cultured L2 cells, and was detected by indirect immunofluorescence on MHV-3-infected cultured YAC cells. In addition, it conferred a significant protection against MHV-3-induced acute disease, if injected intraperitoneally to C57BL/6 mice before inoculation with MHV-3.

Animals↗
PubMed1987

The association of the rabies glycoprotein with liposome (immunosome) induces an in vitro specific release of interleukin 2.

BALB/c mice were primed by receiving a unique intraperitoneal injection of rabies virus antigens presented as complete inactivated virus (P.V. strain) or as purified glycoproteins either in the aggregated form or in physical combination with liposomes (i.e., in the form of "immunosomes"). The splenocytes of these mice were restimulated, 6-15 days after priming, in culture with rabies virus antigens, and antigen-specific IL-2 production was measured. It was found that rabies antigens presented as immunosomes were as active as the inactivated virus, whereas equivalent amounts of purified glycoproteins were inactive. The optimal amounts of rabies immunosomes used for priming was found to be 0.5 to 0.05 micrograms per mouse.

Animals↗
PubMed1987

Drug-concentration dependent sensitivity to lysis by antibody and complement, of adriamycin- or mitomycin-treated murine lymphoma cells.

Murine lymphoma cells (RDM4) were pretreated in culture, with Adriamycin (ADM) and with Mitomycin C (Mit C), at different concentrations, for 20 h and carefully washed. In a first series of experiments, they were labelled with 51Cr and used as target to the lytic action of alloantiserum and complement (Ab + c), as appraised by the specific 51Cr release test. It was found that exposures of the prospective target cells to high drug concentrations (e.g. 32 micrograms/ml of ADM or 20 micrograms/ml of Mit C) enhanced their susceptibility to Ab + c killing, whereas exposures to low concentrations (i.e. 0.1 microgram/ml of ADM, or 1 microgram/ml of Mit C) protected them from Ab + c mediated lysis. In a second experimental series, similarly treated RDM4 were pulsed with 3H-TdR after their exposure to Ab + c. In this case, the cytotoxic effect was appraised as "inhibition" of isotope incorporation. Using this second criterion, the protective action of pretreatment with low drug concentrations was confirmed, and was particularly clearcut in the case of ADM. The protective effect of pretreatment with low concentration of ADM (0.1 microgram) was also confirmed in vivo, with the "Winn assay".

Animals↗
PubMed1987

Study of CTL and LAK contacts to target cells after treatment with mitomycin C and adriamycin.

We tried to understand the role of Mitomycin C and Adriamycin in the increased killing of target cells by Cytotoxic T lymphocytes (CTL) and lymphokine activated killers (LAK). For this purpose, we used an objective method allowing quantitative evaluation of the roughness of cell contours on electron micrographs. We compared the folding of the membranes of LAK and CTL as well as conjugated targets exposed to different treatments. We demonstrated first that CTL and LAK displayed similar morphological patterns: the killer cells were more villous than targets in the free areas, and second that the former cells exhibited significant smoothing on the areas of contact with these targets. These results suggest that the binding process (as distinct from the recognition step) is dependent on killer properties which are the same in CTL, LAK and probably NK cells.

Animals↗
PubMed1986

Modification, by a poly I:C injection, of organ distribution of intravenously injected murine lymphoma cells and of blood coagulability.

51Cr-or 111In-labelled murine lymphoma cells were injected IV in control and poly I:C-treated mice. The organ distribution (lung, spleen, liver) of radioactivity was measured 2 h after injection. The results showed that if cell injection was performed 1 day after poly I:C treatment, the modifications of organ distribution did not fit with the expectations from a reinforcement of the NK function in vivo. In NK-suppressed mice, poly I:C affected the distribution of radioactivity in spleen and liver in the same manner as in normal mice, suggesting that the action does not entirely depend on the NK system. Additionally to that, poly I:C injections affected coagulability of the plasma from treated mice, by prolonging the coagulation time. It is concluded that poly I:C exerts a complex action on circulation and fixation of lymphoma cells.

Animals↗
PubMed1986

Enhancement of murine lymphoma cell lysability by CTL and by LAK cells, after treatments with mitomycin C and with adriamycin.

Murine lymphoma cells (RDM4) were treated, in culture, with adriamycin (ADM) and with mitomycin C (Mit C) at various concentrations for 20 h. They were then used as 51Cr-labelled target cells and tested for their sensitivity to the killing action both of specifically allosensitized cytotoxic T lymphocytes (CTL) and of lymphokine-activated killer (LAK) cells. They were also used as "cold target" inhibitors, in cytotoxicity assays involving CTL or LAK and 51Cr-labelled target cells. The results showed that treatments with different concentrations of Mit C enhanced the sensitivity of RDM4 cells to the killing actions of both CTL and LAK cells. ADM slightly enhanced sensitivity to the killing action by CTL, but to a much lesser extent than Mit C did. However, ADM proved to be almost as efficient as Mit C in its sensitizing action, in the case of lysis by LAK cells. Treatments with both drugs did not seem to modify the capacity of RDM4 cells to act as "cold target competitors" in cytotoxicity assays involving CTL killers, but did so in experiments involving the lytic action exerted by LAK cells.

Animals↗
PubMed1986

Production of human and murine interleukin-2 by toxic shock syndrome toxin-1.

Toxic shock syndrome toxin-1 (TSST-1), isolated from Staphylococcus aureus strains associated with toxic shock syndrome (TSS), is known as a potent mitogen and interleukin-1 inducer. The potential of TSST-1 as an interleukin-2 (IL-2) inducer was tested on human peripheral blood lymphocytes (HPBL) and murine spleen lymphocytes (MSL). These cells were incubated with TSST-1 and the supernatants analysed for IL-2 production. Preincubation of IL-2-dependent indicator cells (IC) with a monoclonal antibody specific for murine IL-2 receptors inhibited their proliferation by supernatants of TSST-1-treated MSL, thus strongly suggesting that they contain IL-2. The concentrations of TSST-1 required for HPBL or MSL to produce IL-2 ranged between 10(-1) and 10(-4) micrograms/ml. The amount of IL-2 units/ml varied little from one experiment to another. In contrast, IL-2 production by PHA-stimulated HPBL or Con A-stimulated MSL showed great variability and dependence on mitogen concentration. T-cell depleted MSL exposed to TSST-1 produced less IL-2. Experiments with germ-free mice and TSST-1-primed mice demonstrated that IL-2 production is not related to TSST-1 antigenicity.

Adult↗
PubMed1984

Induction of natural killer cells and interferon during mouse hepatitis virus infection of resistant and susceptible inbred mouse strains.

Following infection by mouse hepatitis virus (JHM strain), an induction of natural killer (NK) cell activity was observed in C3H mice, which are considered to be sensitive to JHM virus infection. In contrast, mice of the resistant SJL strain did not show any increase of NK cell activity after JHM virus infection. However, infection of both SJL and C3H mice with mouse hepatitis virus type 3 (MHV3) resulted in an increase of NK level, comparable to that observed with the JHM virus infection in the C3H strain. No significant differences were observed in the NK cell activity of the peritoneal exudate or spleen cells of infected mice. Low levels of interferon were detected in serum or peritoneal exudate of C3H mice infected with JHM virus 18 or 24 hours before, but no detectable early interferon production was found. Also no interferon could be detected in the resistant SJL mice. After JHM virus infection, the number of peritoneal exudate cells (PEC) was increased significantly in C3H mice but not in SJL mice. Macrophages obtained from the C3H mice supported virus replication, whereas SJL macrophages did not. Our data suggest that NK cells do not play a role in the resistance of SJL mice against JHM virus infection but may participate in the defence mechanisms against this virus in C3H mice.

Animals↗
PubMed1984

H-2 control of polyadenylated mRNA production in the spleen of mice injected with Brucella antigens.

RNA was extracted from the splenocytes of Brucella abortus antigen stimulated mice and of control mice. The proportion of chromatographically separated polyadenylated 11.2S mRNA, was determined. With the technique used, only stimulated mice exhibited significant amounts of this RNA species. The highest level was reached 1 day after the stimulation, and the decay from this level presented an oscillatory form during the 4 weeks following the injection. In two different genetic backgrounds, H-2b mice did not respond to the stimulus, in contrast to H-2a and H-2f mice. H-2b/H-2f heterozygotes behaved roughly as intermediate between H-2b and H-2f mice. This genetic control seems to parallel the genetic control of some Brucella-induced, thymus-dependent events previously described.

Animals↗
PubMed1984

Cell surface modifications with trifluoromethyl dinitrophenyl-soluble protein conjugates: immunogenic role of noncovalently bound hapten.

Bovine serum albumin (BSA) was derivatized, under mild conditions, with trifluoromethyl-dinitrophenyl (CF3-DNP), a haptenic group cross-reacting with trinitrophenyl (TNP). High-field nuclear magnetic resonance of fluorine (19F-NMR) permitted to calculate the number of covalently and noncovalently bound haptenic groups per BSA molecule. Further dialysis against paratoluene sulfonic acid permitted to obtain CF3-DNP-BSA conjugates from which noncovalently bound hapten had been removed. Soluble conjugates containing 4 covalently bound plus 1 noncovalently bound hapten groups, or only 4 covalently bound groups, were added to splenocytes in culture. These splenocytes, after such treatments, were added to effector lymphocytes in a 5-day culture aimed at the generation of cytotoxic T lymphocytes (CTL) against the CF3-DNP-induced cell surface modification antigens. It was found that only the BSA conjugates that contained noncovalently bound haptens were able to generate CTL against target cells whose surface had been directly modified with CF3-DNP, whereas BSA bearing only covalently bound hapten groups were not. Replacing BSA by human serum albumin, or CF3-DNP by TNP, gave comparable results. Thus, under the conditions used, haptenic groups covalently bound to their soluble carrier protein did not generate hapten-dependent CTL, but noncovalently bound or free haptenic groups at very low concentration were able to do so.

Antigens, Surface↗