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J M Rojo

Publications and source records attributed to J M Rojo.

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

Physical association of CD4 and the T-cell receptor can be induced by anti-T-cell receptor antibodies.

CD4 can physically associate with the CD3-T-cell receptor complex as visualized in cocapping experiments. This association occurs when the T-cell receptor is cross-linked by certain anti-variable region antibodies that appear to induce a conformational change in the receptor such that it associate with CD4. Similar association has been observed in earlier studies with the same cloned helper T cell when the physiological ligand, antigen-class II major histocompatibility complex molecule, is bound by the T-cell receptor. The ability of anti-T-cell receptor antibodies to induce the T-cell receptor-CD4 association correlates with a 100-fold increase in the ability of the antibody to activate the T cell. This suggests that the complex of CD4 and the T-cell receptor act synergistically in T-cell activation, thus readily explaining the commonly observed association of CD4 expression with class II major histocompatibility complex-restricted antigen recognition. This association could also play a role in infection by human immunodeficiency virus.

Animals↗
PubMed1989

Asymmetry in the recognition of antigen: self class II MHC and non-self class II MHC molecules by the same T-cell receptor.

One of the most puzzling observations in immunology is the very high frequency of T cells reactive to non-self MHC molecules. Earlier studies from our laboratory suggested that the same receptor on a cloned T-cell line recognized both self-class II MHC: antigen complexes and non-self class II MHC, the latter at a significantly lower affinity. This suggested that alloreactivity resulted from low affinity cross-reactions of the T-cell receptor to a ligand presented at high multiplicity. The present studies address the question of whether these two ligands are recognized symmetrically by this receptor, and of whether different subsites in the receptor recognize both classes of ligands equally. In the present studies, we have greatly extended our analysis of T-cell receptor recognition of antigen: self class II MHC and non-self class II MHC. Using Fab fragments of monoclonal anti-T-cell receptor antibodies as monovalent competitive antagonists of T-cell activation, the response of cloned H-2k T-cell line D10 to conalbumin: I-Ak and to the allogeneic ligands I-Ab,v,p,q was analyzed with monoclonal antibodies directed at 3 clonotypic epitopes and one on V beta. These studies confirmed our earlier finding that D10 activation by antigen: self class II MHC is more difficult to inhibit with clonotypic Fab fragments binding to three distinct clonotypic epitopes than are responses to non-self MHC. More importantly, the Fab fragment of anti-V beta monoclonal antibodies preferentially inhibit activation by antigen: self class II MHC, and do so more efficiently than expected, based on the numbers of molecules of Fab bound.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

The biologic activity of anti-T cell receptor V region monoclonal antibodies is determined by the epitope recognized.

We have used 10 independently isolated mAb reactive with the Ag R on a cloned Th cell line to map three distinct epitopes and three subepitopes on the R. One of these epitopes is clearly on the V beta 8 region, as it is defined by the antibodies KJ-16 and F23.1, known to react with the V beta 8 family of variable regions, and a functional rearranged V beta 8 gene has been cloned from this cell line. Antibodies directed at a second epitope, believed to be on V alpha because it is unaffected by anti-V beta antibodies, are completely inhibited from binding by monoclonal anti-CD3 epsilon-chain antibodies. Because the cloned Th cell line used, D10.G4.1, responds to soluble monoclonal anti-TCR antibodies, it has been possible to compare the binding of anti-R antibodies with their ability to activate this cloned T cell line. We find that for antibodies all specific for the same or a closely related epitope, activation is proportional to binding, by using antibodies that differ by greater than 100-fold in avidity for the R. By contrast, antibodies directed at different epitopes on the R differ markedly in their ability to activate the D10.G4.1 cell line. We have tested whether these differences reflect differences in the orientation of cross-linking the TCR or possible conformational changes induced in the R by the antibodies, and our data support the latter hypothesis as an explanation for the differences in activation potency between antibodies.

Animals↗
PubMed1987

Isoprinosine restores in vitro T lymphocyte functions of cyclophosphamide immunosuppressed mice.

The effect and the mechanism of action of isoprinosine has been investigated in several models of in vitro activation of lymphocytes. Isoprinosine added to spleen cell cultures enhanced lymphocyte proliferation induced by concanavalin A or allogeneic stimulation as well as the generation of allospecific cytotoxic T cells. The effect of isoprinosine on T lymphocyte proliferation in vitro was specially marked when mice were treated with cyclophosphamide (75-200 mg/kg) 16-24 h before the onset of cultures. No effect was observed on B cell proliferation to LPS. Addition of inosine or adenosine also enhanced proliferation of cells from both normal and cyclophosphamide treated mice. Isoprinosine and inosine and, more markedly, adenosine, augmented interleukin-2 activity in concanavalin A supernatants of spleen cells from the same animals.

Animals↗
PubMed1987

Immunoferon (AM3) enhances the activities of early-type interferon inducers and natural killer cells.

The "in vivo" effect of Immunoferon (AM3) on the production of interferon (IFN) and natural killer (NK) activity in young and old mice was studied. Although AM3 is not an IFN inducer by itself, enhancements in the serum IFN levels were produced when drug was associated to Newcastle disease virus or bacterial lipopolysaccharides as IFN inducers. This effect appeared to be dependent on the time lapsed between the inducer agent and drug. In addition, a significant stimulating effect on NK cell activity was also produced by AM3 treatments. This effect could be a consequence of a marked IFN induction and/or a modifying effect in prostaglandin synthesis.

Animals↗
PubMed1986

Enhancement of lymphocyte proliferation, interleukin-2 production and NK activity by inmunoferon (AM-3), a fungal immunomodulator: variations in normal and immunosuppressed mice.

The in vivo effect of Inmunoferon (AM-3), a glycophosphopeptide of fungal origin, has been studied on T and B lymphocyte mitogenesis, Interleukin 2 (IL-2) synthesis and natural killer (NK) activity. Inmunoferon (30 mg/kg/day) was administered to several groups of mice 2, 3 or 7 days/week for 2 weeks, and its effect assessed on day 15 of treatment. Every treatment assayed enhanced IL-2 and NK activity in the spleen. The greater effect was produced by daily administration of the immunomodulator. No enhancement was found in mitogen-induced proliferation of T and B lymphocytes. Similar treatments with Inmunoferon enhanced NK activity in the spleens of mice treated with 250 mg/kg cyclophosphamide. In addition, mitogenic responses of T lymphocytes, but not IL-2 production, were also increased in immunosuppressed mice after treatment with the immunomodulator.

Animals↗
PubMed1986

In vivo effect of isoprinosine on interleukin-2 production, lymphocyte mitogenesis and NK activity in normal and cyclophosphamide immunosuppressed mice.

The in vivo effect of isoprinosine on IL-2 production, mitogen-induced proliferation and NK activity of lymphocytes from normal as well as cyclophosphamide (CY) treated mice has been investigated. Isoprinosine was given in a single dose (50 mg/kg or 5 mg/kg) to normal or CY treated mice (250 mg/kg i.p. simultaneously to isoprinosine). An enhancement of T lymphocyte proliferation and IL-2 production was observed in both cases. There was no correlation between the small effect observed in T lymphocyte proliferation and the enhancement of IL-2 levels found in the supernatants of Con A activated spleen cells, specially in normal mice. Administration of isoprinosine every day (50 mg/kg) augmented Con A induced mitogenesis, IL-2 production and NK activity in animals treated with cyclophosphamide, but not in normal mice. Isoprinosine could be of interest in a combined treatment with immunosuppressants for the restoration of certain immune functions. The effect of isoprinosine on immune responses may be mediated in part by changes in IL-2 activity.

Animals↗
PubMed1986

Influence of mouse genotype on passive systemic anaphylaxis by immune complexes.

The influence of mouse genotype on passive systemic anaphylaxis (PSA) by immune complexes was studied. PSA was induced by using Brucella abortus endotoxin as the antigen and rabbit anti-Brucella endotoxin antisera. Experiments using syngeneic mice as well as mice congenic for H-2 showed that the H-2 haplotype influenced the sensitivity of mice to PSA. Among the H-2 haplotypes studied, H-2b was the most sensitive, followed by H-2k and H-2d. Experiments using passive transfer of serum as well as the complement inhibitors suramin and flufenamic acid indicated that variations in complement levels under control of H-2 may be responsible for the effects described. Cyproheptadine, a blocker of serotonin and histamine receptors, and imidazol-alpha-ketoglutarate, an inhibitor of thromboxane synthesis, inhibited PSA, indicating that platelet aggregation, possibly mediated by activated components of the complement cascade, is an important feature in the development of PSA reactions in this system. Differences between strains for protection by cyproheptadine and for the effect of complement inhibitors indicated a role of early components of the classical pathway in this model.

Anaphylaxis↗
PubMed1985

Immunomodulatory activity of anti-atherogenic drugs: effects on blastogenesis, humoral response, delayed hypersensitivity and passive anaphylaxis by immune complexes.

The effect of several anti-atherogenic drugs (ticlopidine, nicotinic acid and etofibrate) on immune responses and immune complex anaphylaxis has been studied in mice. All the drugs enhanced the activation by concanavalin A, phytohemagglutinin, and lipopolysaccharide of lymphocytes taken from treated animals. Contact hypersensitivity to trinitrochlorobenzene was inhibited by similar treatments with the same drugs, possibly through inhibition of the efferent phase of the reaction. Nicotinic acid produced a slight enhancement of antibody responses to sheep erythrocytes, whereas etofibrate inhibited the response at the highest dose studied. In addition, treatment with these drugs variably protected the mice from anaphylactic shocks induced by immune complexes. Marked protection was also observed using the antiserotoninic, cyproheptadine. These results indicate that drugs used to prevent atherogenic processes modulate different proliferative and effector immunological reactions.

Anaphylaxis↗
PubMed1985

Yq deletion (q11.21) in a H-Y+ azoospermic male.

A large deletion of the long arm (q11.21) of chromosome Y without mosaicism was found in a 28-year-old male. The proband has a normal height and normal male habitus but with azoospermia. The occurrence of H-Y+ level, azoospermia and loss of a great portion of euchromatic Yq in the proband is analyzed.

Adult↗
PubMed1984

Inhibitory mechanisms of 5-fluorodeoxyuridine on mitogen-induced blastogenesis of lymphocytes.

5-Fluorodeoxyuridine inhibited DNA synthesis of mitogen-stimulated T and B cells as determined by either incorporation of 3H-thymidine to the cells or measure of DNA content in the cells by microdensitometry. 5-Fluorodeoxyuridine concentrations necessary to inhibit DNA synthesis by 50% in the stimulated cultures were high (2 micrograms/ml and 7 micrograms/ml for B and T cells, respectively). Addition of exogenous thymidine (100 micrograms/ml) partially reversed the inhibition of DNA synthesis by 5-fluorodeoxyuridine (10 micrograms/ml). These data indicate that lymphocytes possess a mechanism of resistance to inhibition of thymidilate synthetase by 5-fluorodeoxyuridine. On the other hand, the inhibition of mitogen-induced blastogenesis is not only mediated by an effect on thymidilate synthetase but could also be mediated by other mechanisms, such as inhibition of nucleic acid precursor transport into the cells.

Animals↗
PubMed1984

[Quantification (by nomograms) of physiopathological parameters in an experimental model of passive anaphylaxis caused by immune complexes].

Pharmacological changes in a model of passive anaphylaxis by immune complexes in mice have been studied. The results have been evaluated by nomograms to overcome the difficulties observed when using classical criteria as 50% lethal dosis or 50% infective dosis in experimental models which do not allow serial dilutions of the reagents. Mean lethal time, maximal pathogenic capacity and relative survival time can be easily determined, allowing the comparison of the immunopharmacologic protection for each administration schedule. By these criteria, we have observed a different degree of anaphylactic reaction depending on the genetic background of the hosts as well as a protection against anaphylactic shock using the antiserotoninic cyproheptadine and, to a lesser extent, by the platelet antiaggregant ticlopidine.

Anaphylaxis↗
PubMed1984

Positive selection by "panning" of B lymphocytes using unfractionated anti-immunoglobulin antiserum.

A simple method allowing a positive selection of mouse B lymphocytes by "panning" has been achieved using rabbit anti-mouse immunoglobulin antisera without further purification. Plastic petri dishes were coated with the gamma-globulin fraction of normal mouse serum and then incubated with excess rabbit anti-mouse gamma globulin antiserum. These plates were then used for the selection of B lymphocytes by incubation of spleen cells in the plates. The adherent cells wee above 95% B lymphocytes as judged by immunofluorescence staining, proliferated in response to bacterial lipopolysaccharide and were not stimulated by concanavalin A.

Animals↗
PubMed1983

Inhibition of T and B lymphoblastic response by mithramycin, dacarbazine, prospidium chloride and peptichemio.

Four different cytostatic compounds (prospidium chloride, peptichemio, dacarbazine and mithramycin) have been assayed for their effect on lymphoblastic transformation of spleen cells from mice. The drugs did not affect cell viability at concentrations lower than 0.1-0.2 micrograms/ml (peptichemio and mithramycin) or than 10-20 micrometers/ml (prospidium chloride and dacarbazine). Except for peptichemio, which did not show any marked effect, these cytostatics acted more actively on B cells than on T cells at concentrations of drug not affecting lymphocyte viability. Mithramycin was the most active inhibitor of the mitogen-induced DNA synthesis in the cell. Concentrations of this drug to inhibit the blastogenic response to 50% (IC50) were lower than 0.1 microgram/ml. Inhibition of mitogenesis was less pronounced in the case of dacarbazine (IC50 = 50 and 10 micrograms/ml for T and B cells, respectively), prospidium chloride (IC50 greater than 50 and 50 micrograms/ml for T and B cells) and peptichemio (IC50 = 0.25 and 0.5 microgram/ml for T and B cells, respectively.

Animals↗
PubMed1983

Enhancement and restoration of contact sensitivity reactions by isoprinosine.

Isoprinosine (50 mg/kg i.p.) increased the ear swelling reaction in mice sensitized with trinitro-chlorobenzene (picryl chloride) and challenged with the same agent. Enhancements were observed when the drug was administered either simultaneously to the sensitization or to the challenge with picryl chloride. Similar results were obtained when lymphoid cells from sensitized animals were transferred i.v. to normal animals which were then challenged with picryl chloride. Using the same cell transfer system, we found that treatment of cell donors with Isoprinosine (50 mg/kg/day, i.p.) counteracts the inhibition induced by cyclophosphamide. Isoprinosine (50 mg/kg/day, i.p.) inhibited also the generation of antigen-specific suppressor cells induced by picryl-sulfonic acid as shown by transfer to normal recipients of suppressor cells together with lymphoid cells from sensitized animals. These results indicate that Isoprinosine enhances normal contact sensitivity reactions and can counteract, under certain circumstances, antigen-specific as well as nonspecific immunosuppression.

Animals↗
PubMed1983

Modulatory effect of isoprinosine on lymphocyte proliferative response under immunodepressive conditions.

In the present work the effect of Isoprinosine on the mitogenic responses of T and B lymphocytes has been studied. We have found that Isoprinosine can enhance in vitro the response to Concanavalin A. This enhancement was more apparent in cell cultures showing an initially low blastogenic response. In low responses artificially induced by treatments in vivo with cyclophosphamide, our results indicate that Isoprinosine, administered in vivo, does not enhance the response to Con A of treated mice. However, addition of Isoprinosine (75 micrograms/ml) to cultures of spleen cells from mice previously treated with cyclophosphamide enhanced the suppressed response up to normal levels. Neither in vivo nor in vitro Isoprinosine treatments increased the response of lymphocytes to lipopolysaccharide, but usually inhibited the blastogenesis of B cells.

Adjuvants, Immunologic↗