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Biomedical subjects

B D Brondz

Publications and source records attributed to B D Brondz.

At least 19 recordsLinked to original sources
PubMed1997

The functional transformation of cytotoxic lymphocytes into T-suppressors under the influence of two mediators.

A set of CTL-lines in the system differing in the whole H-2 complex, as well as in distinct subregions of H-2, was established. These lines were routinely tested in Cr51-release assay to insure that they retained lytic activity and antigen-specificity. The result of the interaction of CTL with H-2Kb-molecule and alpha1-thymosine was transition of CTL into a reversible state of anergy. A high concentration of alpha1-thymosine is necessary for this transition. Anergic CTL caused specific suppressor activity that is functional if transformation of CTL into T-suppressors took place.

Animals↗
PubMed1995

Immunosuppressive factor from liver induces apoptosis in thymoma EL-4 cells but not normal MHC class II-specific T lymphocytes.

An endogenously produced immunosuppressive factor (ISFnp, immunosuppressive factor-neutral protein), inducing a decrease in viability of thymoma EL-4 cells in vitro, was isolated from murine liver using ion exchange, gel filtration and hydrogen-bonding chromatography. Polyclonal rabbit antibodies against this factor were developed and attached to periodate-activated Sepharose CL-6B. The immunoaffine sorbent obtained significantly depleted the biological activity of ISFnp from tested fractions. The factor shows liver-specific location, an M(r) of about 70-80 kDa and consists of 2 subunits (40 and 42 kDa) as determined by SDS-PAGE and Western blotting. ISFnp induced DNA degradation in EL-4 cells similar to the cleavage of DNA onto olygonucleosomal fragments in dexamethasone-treated thymocytes. This DNA degradation preceded lysis of thymoma cells, suggesting an induction of apoptosis in ISFnp-treated EL-4 cells. Addition of the factor into primary mixed lymphocyte culture (MLC) strongly inhibited proliferative response but failed to induce any decrease in the ability of normal MHC class II-specific alloreactive cells to respond in the secondary MLC. Moreover, addition of ISFnp into primary MLC on the peak of proliferative response resulted in augmentation of secondary responses of primed cells as compared with the same quantities of primed cells from untreated cultures. These results suggest a possible role of liver both in deletion of transformed clones of T lymphocytes and formation of allospecific memory T cells.

Animals↗
PubMed1995

Peptides of a major histocompatibility complex class I (Kb) molecule cause prolongation of skin graft survival and induce specific down-regulatory T cells demonstrable in the mixed lymphocyte reaction.

Six individual peptides of the major histocompatibility complex (MHC) class I molecule H-2Kb were synthesized. Intravenous injection of peptide 6 into mice prolonged the survival of Kb (BL/6 or B10.MBR) skin grafts on allogeneic R101 and B10.AKM mice, respectively. This was specific, as control skin grafts from Kk (B10.BR) or Kd (DBA/2) donors, respectively, were rejected at the same time in both control and peptide-treated mice. The optimal doses for peptide 6, which is from the alpha 2 domain, were defined. The test system was the inhibition of proliferation in vitro of naive lymph node cells by syngeneic mitomycin c-treated spleen cells from R101 mice preimmunized with irradiated stimulator splenocytes of Kb (BL/6) origin. Down-regulation was specific, as proliferation in response to third-party allogeneic stimulator Kk (B10.BR) splenocytes was not inhibited. Of the six peptides of H-2Kb tested, potent down-regulatory cells were induced by peptides 2 (alpha 1 domain) and 5 and 6 (alpha 2 domain). The greatest down-regulatory activity was obtained by giving peptide 2 to mice that had already been immunized against H-2Kb by injecting EL4 cells. Under the same conditions, injecting peptide 2 did not induce any cytotoxic T cells. In contrast, specific cytotoxic lymphocytes (CTL) were induced when cells from primed mice were incubated for 4 days with heated stimulator cells from BL/6 mice. The data suggest that peptides from MHC class I molecules activate precursors of down-regulatory T cells, but not of CTL, and this may explain their ability to prolong skin allograft survival.

Amino Acid Sequence↗
PubMed1995

[Use of histocompatibility class I molecule peptides for in vivo induction of specific T-suppressors in allogenic systems and prolongation of mouse skin graft life].

Six synthetic peptides were selected for the individual molecule H-2Kb of the major histocompatibility complex class 1. Optimum conditions were elaborated for the induction of specific suppressor T cells in vivo by peptide 6 (alpha 2 domain) in an intravenous dose of 33 micrograms to the tail vein or 100 micrograms to the orbital sinus, followed by testing the suppressor activity in inhibiting in vitro proliferation in the three-cell MLC in response to irradiated cells of the stimulator Kb (BL/6) in the absence of suppressed response to the foreign stimulator Kk (B10.BR). Out of 6 different peptides of the same molecule H-2Kb, suppressor T cells were induced effectively by peptides 2 (alpha 2-domain), 5 and 6 (alpha 2-domain), while the high efficiency of suppressors is realized by memory cells along with peptides 2. Under the same conditions, in vivo peptide immunization did not induce cytotoxic T lymphocytes at all. In contrast, CTL were specific in their high efficiency where memory cells were in vitro pretreated with stimulators of warmed BL/6 cells. Intravenous administration of peptide 6 to mice gave rise to prolongation of Kb (BL/6 or B10.MBR)-induced skin transplantation during the transfer from allogenic murine R101 and B10.AKM, respectively, but without the terms of skin prolongation at all with the stranger donors Kk (B10.BR) or Kd (DBA/2).

Amino Acid Sequence↗
PubMed1994

L3T4+ but not LYT2+ T-helper cells are required for in vitro maturation of in vivo primed T cells in the cytotoxic response to MHC class I disparate cells following footpad immunization.

The induction characteristics of major histocompatibility complex (MHC) class I-specific cytotoxic T lymphocytes (CTL) after footpad immunization were studied. Primary CTL were generated in the regional lymph nodes of C57Bl/6 mice by footpad injection with 10(7) irradiated (2000 rad) spleen cells from MHC class I mutant mouse strain (bm1) followed by a short in vitro culturing without antigen. The requirement of accessory cells and L3T4+ T cells during in vitro maturation of in vivo primed CTL precursor (CTLp) was shown. Moreover, using inhibitory antibodies, the need for IL-2 and IL-4 for in vitro maturation of CTL was established. We have suggested that accessory cells act at the level of L3T4+ T cells which in turn non-specifically up-regulate the CTL response through the production of growth and differentiation factors. Thus, the T-helper population of L3T4+ but not Lyt2+ phenotype appears to be recruited in the in vitro maturation of in vivo primed CTLp in a given system. Possible mechanisms of this phenomenon are discussed.

Animals↗
PubMed1994

Generation of specific antitumor cytotoxic T-lymphocytes in monoculture can be inhibited by T-suppressors from tumor-bearing mice.

A new model for the generation of specific antitumor cytotoxic T lymphocytes (CTL) was proposed. In contrast to other models, it allows to generate secondary effector CTL (CTL-2) without tumor stimulator cells in vitro (in monoculture). C57BL/10 mice or/and C57BL/6 mice were immunized by injection with gamma-irradiated syngeneic tumor cells into the footpads. For estimation of cytotoxic activity, chromium-51 release assay was used. It has been shown that effector CTL were absent in the lymph nodes after 1-fold as well as 2-fold immunization. Cytotoxic cells have not been found in 1-fold immunization even after maturation of the lymphocytes in monoculture. Specific CTL were detected only after secondary immunization and subsequent cultivation in vitro. Effector cells had Thy1.2, CD8+, CD4- phenotype. Presence in vitro of exogenous recombinant interleukin 2 (rIL-2) was needed for the generation of CTL-2 against Mech-11 sarcoma but not against EL4 lymphoma. The spleen cells from B10 mice with progressively growing Mech-11 tumor specifically suppressed the maturation of CTL-2 against Mech-11 in monoculture. Since suppression took place in the presence of exogenous rIL2 in monoculture, it was suggested that suppression was not resulted by negative influence of the suppressor cells upon endogenic IL-2 production. The treatment of the suppressor cells with monoclonal antibody (Mab) against Thy1.2 as well as against CD4 or CD8 markers plus complement (C') considerably decreased Ts activity. Obviously, two distinct subsets of T-lymphocytes were required for suppression.

Animals↗
PubMed1993

Intravenous injection of allogeneic cells can prime T-lymphocytes with cytotoxic activity.

The possibility of specific cytotoxic T-lymphocyte (CTL)2 induction was shown upon intravenous (i.v.) immunization of mice with 9 x 10(7) irradiated (2000 rad) allogeneic splenocytes. The induced CTL express the cell surface markers Thy1.2+, L3T4- and Lyt2+. No correlation between the level of cytotoxic activity and the ability to inhibit proliferation was shown in populations of lymphocytes, primed both by i.v. immunization and in mixed lymphocyte culture (MLC). The possible role of cytotoxic activity in down-regulation of the immune response is discussed.

Animals↗
PubMed1993

Utilization of the MHC class I (H-2Kb) purified molecule and its synthetic peptides for inhibition of Kb-specific suppressor T cells and their induction in vivo by the MHC peptides.

Six synthetic peptides of the MHC class I molecule corresponding to individual H-2Kb participants in amino acid sequences of domains alpha 1 (peptide 1 and 2) and alpha 2 (peptides 3, 4, 5, 6) were selected. Kb-specific suppressor T cells (Ts) were induced in vivo in mice, then pretreated with a set of peptides and assayed by proliferation decrease in a three-cell lymphocyte culture (MLC). The effector function of Ts was abolished by the complex of the alpha 2-domain peptides (but not by the alpha 1-domain peptides) and decreased by particular peptides separately (4, 5, 6) of the alpha 2-domain. Both alpha 1- and alpha 2-domain peptides, added in high concentration, decreased otherwise efficient enrichment of Ts during the absorption-elution procedure on the syngeneic macrophage (M psi) monolayers. A similar significant effect was observed using the purified Kb molecule (100 micrograms/ml) in the allogeneic M psi monolayer. Interaction between Ts receptors and some MHC peptides indicates in effector Ts activation in vivo by induction with peptides 5 and 6 of the alpha 2-domain. The fine mechanisms of interaction between MHC class I molecule epitopes and T-cell receptors of each of the T-cell subsets separately are presently being studied.

Amino Acid Sequence↗
PubMed1993

[Effect of the Ly2 molecule on the function of alloantigen-specific effector cytotoxic T-lymphocytes as a function of the variability of their receptors' affinity].

To study T cell receptors' affinity alloantigen-specific anti-K cytotoxic T-lymphocytes (CTL) were divided on fractions by elution from donor K and third-party macrophage monolayers. The functional activity of CTL was suppressed by anti--Ly2 monoclonal antibodies (mAb), 51-Cr-labelled transformed fibroblasts (L-cells) transferred with the H-2K gene were used as targets. The results demonstrate that primary CTL enriched on third-party macrophage monolayers are the most sensitive to anti-Ly2 mAb. T-cells exhausted on third-party monolayer and then enriched on donor monolayer were resistant to treatment with the mAb. Secondary CTL enriched on donor monolayer were resistant to treatment with anti-Ly2 mAb even should they were not exhausted on third-party monolayer. These results show that Ly2 (CD8) molecule plays an essential role in the interaction of CTL with MHC class I molecule only if T-cell receptor has low affinity.

Animals↗
PubMed1993

[Monoclonal antibodies to the beta-chain of the LFA-1 molecule promote an increase in the cytotoxic index of effector lymphocytes and stimulate their proliferation].

The influence of monoclonal antibodies (mAb) to LFA-1 molecule beta-chain on the functional activities of immune splenocyte fractions which were eluted from donor, third party and recipient macrophage monolayers was studied. The splenocyte fractions were treated with the mAb and tested for cytotoxicity and proliferation. MAb to LFA-1 molecule beta-chain (without co-stimulation by other antibodies) were found to stimulate the immune response of the splenocyte fractions in both functional tests. The observed effect might be non-specific. The relationship between the stimulation of proliferative and cytotoxic responses of the immune splenocyte fractions and the treatment with mAb of LFA-I molecule beta-chain remains obscure.

Animals↗
PubMed1993

[The stimulation of the proliferative reaction of immune splenocytes by monoclonal antibodies to the beta-chain of the LFA-1 molecule can lead to an increase in their cytotoxicity].

A system for investigation of relationship between proliferation and cytotoxicity of immune splenocytes fractions stimulated by monoclonal antibodies (mAb) to beta-chain LFA-1 molecule was elaborated. To obtain different proportional contents of effector cells in populations, the immune splenocytes were eluted from donor, third-party, and recipient macrophage monolayers. Cytotoxic indices of effector splenocyte fractions were compared before and after their proliferation in mixed lymphocyte culture. The results do not exclude the role of proliferation in increasing the effector cells proportions in populations stimulated by mAb to beta-chain LFA-1 molecule.

Animals↗
PubMed1992

Application of anti-CD3-treated lymphocytes as stimulator cells in human autologous mixed lymphocyte cultures for generation of autorestricted CD8+ suppressor T cells.

The purpose of the present study was to investigate the application of anti-CD3-treated lymphocytes as stimulator cells in human one-way autologous mixed lymphocyte cultures (MLC) for the generation of suppressor cells. MLC-activated CD4-CD8+ CD16- T cells were non-cytotoxic, while they down-regulated the proliferation of autologous (but not allogeneic) responder lymphocytes in allogeneic test MLC.

Antibodies, Monoclonal↗
PubMed1992

[Mechanisms of immunodeficiency in HIV infection and ways of overcoming it].

Though antibodies against HIV-1 appearing in the course of infection are successfully used for the diagnostic purposes, their accumulation on the earlier step leads to: firstly, to the rapid generation of the immunodeficiency by different mechanisms and secondly, to inefficiency of immunotherapy. One of the causes for immunodeficiency seems to be antibodies which are induced in the HIV-infected person by the HIV peptides homologous to the MHC class II molecules by their amino acid sequences. 73% of HIV-1 positive sera are shown to react with human B-lymphoma cells expressing surface class II molecule. The binding is caused by the antibodies preventing the murine monoclonal anti-HLA.DR Ab interaction with B-lymphoma. Three amino acid sequences are identified in both alpha- and beta-chain of the HLA.DR antigen, these sequences being homologous to HIV-1 gp120 or gp42 molecules for 50 to 70%. Using synthetic peptides it was shown that HIV-1-infected persons contain antibodies which cross-react to the homologous peptides of the HIV-1 and of the MHC class II. It is supposed that such antibodies shield the class II molecule on the surface of their own antigen-presenting cell which may lead to immunodeficiency caused by the anti-HIV-1 antibody.

Acquired Immunodeficiency Syndrome↗
PubMed1992

[T-suppressors from tumor-bearing mice inhibit antitumor cytotoxic T-lymphocytes in monoculture].

The generation of specific antitumor cytotoxic T-lymphocytes (CTL) via 2-fold immunization in vivo and subsequent cultivation without tumor cells (in monoculture) was previously described. The spleen cells from B10 mice bearing progressively growing MX-11 sarcoma suppressed the maturation of CTL specific to MX-11 but not to EL-4 lymphoma in monoculture. It was observed, that the suppression was not the result of the inhibitory effect of suppressor cells upon the IL-2 production, because suppression took place in the presence of the exogenous IL-2 in monoculture. Since the treatment of the spleen cells with MoAb against both L3T4 and Lyt2.2 antigens plus C' considerably decreased the suppressive activity, it was suggested, that two distinct subsets of T-lymphocytes were required for suppression. It might be possible, that the presence of anti-idiotype on the effector suppressors was the cause of the suppressive specificity in the absence of tumor antigens in vitro.

Animals↗
PubMed1992

[Formation of specific antitumor cytotoxic T-lymphocytes in monoculture].

A new model for the generation of specific antitumor cytotoxic T-lymphocytes (CTL) was proposed. In contrast to other models, it allows to generate effector CTL without immunization in vitro. C57BL/10 mice or/and C57BL/6 mice were immunized by injection with gamma-irradiated syngeneic tumor cells into the footpads. For estimation of cytotoxic activity, chromium-51 release assay was used. It has been shown that effector CTL were absent in the lymph nodes in 1-fold as well as 2-fold immunization. Cytotoxic cells have not been found in 1-fold immunization even after maturation of the lymphocytes in monoculture. Specific CTL were detected only after secondary immunization and subsequent cultivation in vitro. Effector cells had Thy1.2+, Lyt2+, L3T4- phenotypes. Presence in vitro of exogenous IL-2 was needed for the generation of CTL against MX-11 sarcoma but not against EL4 lymphoma. We suggest that the release of IL-2 from lymphomas cells could stimulate generation of the effector cells through activation of the endogenous production of IL-2, or due to some other factors.

Animals↗
PubMed1991

Different conditions for generation of non-cytotoxic autorestricted CD4-CD8+ human suppressor T cells and allospecific cytotoxic T lymphocytes in one-way mixed lymphocyte cultures: the role of adherent mononuclear cells.

The purpose of the present study was to investigate the role of adherent mononuclear cells (AMC) in generation of suppressor T lymphocytes (T-Lph) in one-way allogeneic mixed lymphocyte cultures (MLC). Alloantigen-specific cytotoxic T-Lph were generated in MLC predominantly in the presence of stimulator AMC, but not responder AMC. The presence of responder AMC and the absence of stimulator AMC were optimal conditions for generation of non-cytotoxic (through the whole duration of MLC) suppressor T-Lph. These CD4-CD8+ suppressor T-Lph were allononspecific but autorestricted (with responders in test MLC).

CD4 Antigens↗
PubMed1991

The role of T lymphocytes in the immunotherapy of tumours.

The interactions of tumour cells with membrane molecules of T-cell subsets, as well as methods directed towards the enhancement of antitumour immunity, are reviewed in this paper. Special attention is given to the cytotoxic function of lymphokine-activated tumour-infiltrating lymphocytes, to tumour-specific suppressor T cells, and to various causes of decreased expression of histocompatibility antigens on the surface of tumour cells. The different mechanisms underlying selective antitumour immunodeficiencies and possible approaches to the correction of immunodeficiency, to the enhancement of tumour immunogenicity, and to specific immunotherapy are considered in more detail.

Adjuvants, Immunologic↗