IDENTIFICATION OF THE IMMUNE SYSTEM RESPONSIBLE FOR THE SPECIFICITY OF ACTIVELY ACQUIRED TOLERANCE IN MICE.
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Journal Article↗
Biomedical subjects
G Doria
Publications and source records attributed to G Doria.
T cell independent induction of antigen specific suppression of the antibody response.
Immune spleen cells (from mice given 2 x 10(7) HRBC 14 days earlier) when mixed in vitro with carrier-primed syngeneic spleen cells (from mice given 2 x 10(5) HRBC 3 days earlier) are able to suppress the anti-TNP and anti-HRBC PFC response to TNP-HRBC. If immune thymocytes are substituted for spleen cells suppression is not observed. This suppression is antigen specific, resistant to anti-T treatment or x-irradiation, and is exerted by nylon wool-retained cells of the immune spleen cell population. An antigen specific suppressive factor is released from immune spleen cells in culture. Under these experimental conditions, suppression appears to be mediated by a specific product of B rather than T cells present in the immune spleen cell population.
Animals↗
A basic library of microcomputer programs to obtain immunologically relevant information from protein sequences.
A set of simple and interactive BASIC microcomputer programs which may be used to obtain immunologically relevant information from protein sequences is described. Program listings include the computation of structural dissimilarity between two protein sequences (STRUDIS), the predicted secondary structure (CHOUFAS), their expected degree of three-dimensional similarity by correlation of sequence hydrophobicities (HYDCOR) and the location of alpha-helical segments in the three-dimensional protein structure (HELOC). In addition, a general program is described for running mean calculations (RUNMEAN). All programs are listed in a BASIC version for Apple IIE.
Amino Acid Sequence↗
Phosphatidylserine-induced modulation of the immune response in mice: effect of intravenous administration.
The action of phosphatidylserine on the immune response has been examined in mice after the intravenous administration of phospholipid or exposing cultured splenocytes to the action of phosphatidylserine vesicles. Phosphatidylserine (5-25 mg/kg) reduces the T-dependent and the T-independent antibody production. This effect is observed when the phospholipid is injected before (4 h) but not after (24 h) the immunization. The decreased influence of phosphatidylserine injected 24 h before the immunization indicates the reversibility of the action of phospholipid. The effect on the immune system may in part reflect a direct interaction with lymphocytes, since phosphatidylserine (12-60 microM) decreases the production of T-cell growth factors (mainly interleukin-2) elicited by mitogens in cultured spleen cells and reduces the expression of growth factor receptors in the same cells activated by mitogens. In addition, the activity of T-helper cells is found to be reduced in mice receiving the injection of phosphatidylserine. By contrast, the antigen processing and presentation by macrophages is not affected. The data suggest that the intravenous injection of phosphatidylserine vesicles in mice is followed by a transient decrease of lymphocyte activity.
Animals↗
Enhancement of the immune response in mice by Astragalus membranaceus extracts.
Astragalus membranaceus extracts injected into normal mice or mice immunodepressed by cyclophosphamide or radiation treatment or by aging are able to enhance the antibody response to a T-dependent antigen. Optimal conditions for maximum effect have been established in normal C3H/HeJ and (C57B1/10 x DBA/2)F1 mice. Enhancement of the antibody response was associated with increase of Th cell activity in normal and immunodepressed mice. The biological activity of endotoxin-free extracts is dependent on the carbohydrate content.
Adjuvants, Immunologic↗
Melatonin as immunomodulator in immunodeficient mice.
Melatonin, the main hormone of the pineal gland, when chronically injected into young mice or mice immunodepressed by aging or by cyclophosphamide treatment, is able to enhance the antibody response to a T-dependent antigen. The enhancement of the antibody response is associated with increased induction of T helper cell activity and IL-2 production, as evidenced in mice immunodepressed by aging or by cyclophosphamide treatment. These observations suggest that melatonin treatment may be successfully used in the therapy of immunodepressive conditions.
Adjuvants, Immunologic↗
Anti-CTLA-4 human scFv antibodies prevent T-cell activation in transplantation.
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Abatacept↗
Recombinant cytokines as an approach to immune reconstitution in aging.
Aging is characterized by a decreased humoral and cell-mediated immunity to a large variety of exogenous antigens and by an increased propensity to autoantibody production, suggesting an age-related disregulation of the immune system. The decline in immune responsiveness to exogenous antigens has been attributed to thymus involution, consisting of a fall in the capacity to induce intrathymic T-cell growth and differentiation, and also to export mature T cells to the periphery. T-cell activation and secretion of soluble factors have been reported to change with aging, but, as with cytokines, the results are conflicting. We investigated the production of IL-2 and IFN-gamma (Th1 type) and IL-4 (Th2 type) cytokines by mitogen-activated spleen cells from young, adult and old mice and their regulation by the addition of a recombinant cytokine (IL-1 beta, IL-2, IL-3, IL-4, IL-12, IFN-gamma) at varying concentrations. The results indicate that cytokine production can be enhanced only when it is deficient, suggesting the possible use of recombinant cytokines as efficient immunomodulators in age-associated immune disorders.
Aging↗
Effect of melatonin on T helper cell activity.
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Animals↗
Monoclonal suppressor T-cell factor displaying V H restriction and fine antigenic specificity.
The production of stable T-cell clones is essential for the study of T-cell-derived, specific immunoregulatory products and of specific T-cell receptors. T-cell clones have been established by radiation leukaemia virus (RadLV)-induced transformation of suppressor T lymphocytes specific for hen egg white lysozyme (HEL). We report here that culture supernatant obtained from these T-cell clones can, when injected into mice, specifically suppress the anti-HEL antibody response. This monoclonal T-cell product suppresses the antibody response induced by HEL and human lysozyme, but not that induced by ring-necked pheasant egg white lysozyme (REL), thus displaying fine antigenic specificity probably restricted to an epitope involving phenylalanine at amino acid residue 3, present in the N-terminal region of HEL and shared by human lysozyme but absent in REL. The suppression induced by this monoclonal T-cell product is restricted by both H-2 and Igh-1 genes whereas anti-HEL antibodies bearing a predominant idiotype are induced in all mice strains tested, irrespective of their H-2 haplotype or Igh-1 allotype.
Animals↗
Increased levels of NF-kappaB inhibitors (IkappaBalpha and IkappaBgamma) in the intestinal mucosa of Crohn's disease patients during infliximab treatment.
The treatment with infliximab is employed successfully in Crohn's disease (CD) but predictors of efficacy are lacking. Activation of the transcription factor NF-kB has been demonstrated in CD and its inhibition is one of the mechanisms by which anti-inflammatory agents exert their effects. We evaluated the production of TNFalpha by peripheral blood mononuclear cells (PBMC) and the levels of NF-kappaB family molecules in the intestinal mucosa during infliximab therapy in 12 patients. TNFalpha was assayed on supernatants of PBMC culture stimulated with PHA or LPS. Immunohistochemistry was also done on intestinal biopsies. In six patients, Western blot analysis of the NF-kappaB subunit Rel-A, and its inhibitors IkappaBalpha and IkappaBgamma was performed on intestinal biopsies and PBMC. The TNFalpha production by LPS stimulated PBMC showed mild changes, while it was increased by PHA-stimulated PBMC after treatment. The number of inflammatory cells in the intestinal mucosa was reduced (p<0.002) by the treatment. In five out of six cases we detected an increase of the IkappaBalpha and IkappaBgamma)inhibitor levels in intestinal biopsies after treatment. An increase of IkappaB inhibitors levels could be one of the mechanisms by which infliximab decreases NF-kappaB activity and exerts its anti-inflammatory effects.
Adult↗
Synthesis and immunomodulating activity of condensed N-aryl-2-cyano-3-oxo-3-pyrazolyl-propanamides.
A series of condensed N-aryl-2-cyano-3-oxo-3-pyrazolyl-propanamides were synthesized and evaluated for immunomodulating activity following intraperitoneal administration. These new molecules were found to enhance macrophage cytotoxicity and stimulate host mediated antibacterial defences in mice. The compound 3-cyano-3-(1,4-dihydro-1-phenyl-[1]-benzothiopyrano[4,3-c]pyrazol- 3-yl]-3-oxo-N-phenyl-propanamide, chosen for wider pharmacological investigation, proved effective in preventing adjuvant-induced arthritis development in rats.
Adjuvants, Immunologic↗
[Immunoregulation during aging].
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Aging↗
[Effect of preimmunization with its carrier on the cellular secretion of IgM anti-TNP antibodies].
The secretion rate of anti-TNP IgM antibodies has been assessed on spleen cells from unprimed or HRBC-primed mice following immunization with TNP-HRBC. Measurement of the antibodies secretion rate was performed by the hemolytic plaque inhibition assay. HRBC-priming induced greater numbers of anti-TNP PFC/spleen but had no effect on the antibody secretion rate and on its heterogeneity. It is noteworthy that both secretion rate and its heterogeneity were found to oscillate with time after immunization.
Animals↗
[Immunogenetic factors in the onset of experimental tumors].
The influence of immunological and genetic factors on the appearance of experimental tumors has been studied in mice by means of bidirectional selection. We found that the incidence of lymphomas, solid tumors and chronic nephritis is greater in mice selected for low antibody response than in mice selected for high antibody response. These findings suggest that the genes that control the antibody response also regulate life-span and resistance to neoplastic and inflammatory diseases. Similarly, we are carrying out bidirectional selective breeding to obtain two lines of mice, one sensitive and one resistant to the induction of cutaneous papillomas by chemical carcinogens. The two lines differ notably in terms of both percent of incidence and tumor multiplicity. The results of this study demonstrate clearly that resistance and susceptibility to carcinogenesis are subject to polygenic control.
Animals↗