Biomedical subjects

B Susskind

Publications and source records attributed to B Susskind.

7 recordsLinked to original sources

PubMed1996

Cytolytic effector mechanisms of human CD4+ cytotoxic T lymphocytes.

To elucidate mechanisms by which human CD4+ cells mediated cytolytic activity, we studied the expression of cytolytic proteins and the effects of inhibitors and mAbs on T-cell clones. Of seven cytolytic CD4+ clones, three were specific for the HLA-DR17, while four recognized DR18. Anti-HLA-DR mAb and anti-CD4 mAb blocked lysis. In addition, N alpha-p-tosyl-L-lysine chloromethylketone (TLCK), a serine esterase inhibitor, as well as cytochalasin B and monensin, antagonists of secretory pathways, inhibited CD4+ CTLs, whereas the absence of extracellular Ca+2 or the presence of Ca+2 channel blockers partially inhibited cytotoxicity. CD4+ CTLs induced apoptosis of target cell nuclei and membrane damage simultaneously. The CD4+ clones synthesized perforin and granzyme B and expressed the granule-associated protein TIA-1. Our studies indicate that two distinct mechanisms may contribute to cytolysis by CD4+ clones: (1) a Ca+2-dependent mechanism associated with the cytotoxic granules and (2) a Ca+2-insensitive mechanism.

Base Sequence↗

PubMed1993

Analysis of T cell responses in liver allograft recipients. Evidence for deletion of donor-specific cytotoxic T cells in the peripheral circulation.

Analysis of cell-mediated lympholysis in long-term liver allograft recipients indicated that there was a donor-specific unresponsiveness that could not be reversed by the addition of rIL-2 and/or mixed lymphocyte culture supernatant or by nonspecific stimulation of the cultures with PHA. Stimulation of recipient cells with semisyngeneic cells having both donor and third-party HLA antigens failed to reveal the presence of cytotoxic T cells (CTL) specific to the donor, whereas the CTL response to third-party antigens remained normal. Removal of B lymphocytes from the responding cell population did not influence the responses. Furthermore, limiting dilution analysis showed that the liver transplant recipients did not have detectable levels of CTL precursors (CTLp) reactive to the donor antigens, whereas their CTLp to third-party antigens remained normal. Donor-specific CTLp were present before and during the early post-transplant period; these cells were eliminated from the peripheral circulation by 10 mo after transplantation. Taken together, these results indicate that there is a deletion of CTLp specific to donor MHC antigens in the peripheral circulation of long-term liver allograft recipients that may account in part for the success of liver transplantation across MHC barriers.

Adult↗

PubMed1991

A cytotoxic T-lymphocyte clone derived from mice with progressively growing tumors.

Tumor-specific T-cell clones were derived from spleen cells of mice bearing a syngeneic PHS-5 tumor (a P815 mastocytoma mutant). Cells were expanded in vitro and characterized and assayed for activity against the relevant tumor in vivo. Clone cells were CD4-, CD8+ T lymphocytes, as determined by fluorescence activated cell sorting analysis and were specifically cytotoxic against P815 tumor cells in vitro, as shown in chromium 51 release assays. These cells require both antigen and interleukin 2 to proliferate; neither alone is sufficient, even with the addition of interleukin 1. In an experimental P815 liver metastasis model, the adoptive transfer of GD11 or GD11.17 clone cells and injection of recombinant interleukin 2 (7500 U intraperitoneally) 3 days after infusion of tumor cells reduced the number of tumor nodules, while the adoptive transfer of lymphokine-activated killer cells was ineffective.

Animals↗

PubMed1985

Modulation of in vitro cellular immune response by histamine agonists or antagonists in murine species.

The generation of secondary cytotoxic T-lymphocyte (CTL) responses in vitro toward allogeneic P815 mastocytoma cells were suppressed 60-80% when 10(-4) mol/l histamine, 10(-5) mol/l dimaprit (S-[3-(N,N-dimethylamino) propyl]isothiourea dihydrochloride) or 10(-5) mol/l impromidine were present in the culture. Three lines of evidence suggest this observation was a result of an active suppression mechanism and not a result of drug toxicity: Control level activity was obtained when Interleukin-2/T-cell growth factor (IL-2) containing supernatants were added to suppressed cultures. Removal of drug after incubation resulted in control level responses upon reculture. The addition of these H2 agonists to spleen cells from nonimmune animals did not affect the primary CTL response to P815. The effects of H1 and H2 antagonists were also tested in this model. The observed suppression was abrogated by the H2 antagonists cimetidine and mifentidine but not by the H2 antagonist ranitidine nor H1 antagonists, chlorpheniramine, pyrilamine or diphenhydramine. These results suggest regulation of CTL differentiation to alloantigens can be modulated by H2 reactive entities.

Animals↗

PubMed1982

Immunoenhancing activity of NPT 15392: a potential immune response modifier.

NPT 15392, a new immunomodulating compound related to inosine in structure and isoprinosine in action, enhances T-cell dependent immune responses. Antibody responses to sheep red blood cells are augmented two to threefold in mice receiving NPT 15392 while T-cell independent antibody responses to TNP-LPS are unaffected. NPT 15392 does not enhance or alter the number of clonable B cells. This drug also increases cytotoxic T-lymphocyte responses to allogeneic tumor cells but does not alter the number of cytotoxic precursor cells. Immature hematopoietic cell classes (clonable progenitor cells) were also monitored and found not to be influenced by NPT 15392.

Adjuvants, Immunologic↗

PubMed1982

Choices.

Explore the source record for details and available documents.

Adult↗

PubMed1977

An energy-conserving pyruvate-to-acetate pathway in Entamoeba histolytica. Pyruvate synthase and a new acetate thiokinase.

Under anaerobic conditions, cells of Entamoeba histolytica grown with bacteria produce H2 and acetate while cells grown axenically produce neither. Aerobically, acetate is produced and O2 is consumed by amebae from either type of cells. Centrifuged extracts, 2.4 x 106 x g x min, from both types of cells contain pyruvate synthase (EC 1.2.7.1) and an acetate thiokinase which, together, form a system capable of converting pyruvate to acetate. Pyruvate synthase catalyzes the reaction: pyruvate + CoA leads to CO2 + acetyl-CoA + 2E. Electron acceptors which function with this enzyme are FAD, FMN, riboflavin, ferredoxin, and methyl viologen, but not NAD or NADP. The amebal acetate thiokinase catalyzes the reaction acetyl-CoA + ADP + Pi leads to acetate + ATP + CoA. For this apparently new enzyme we suggest the trivial name acetyl-CoA-synthetase (ADP-forming). Extracts from axenic amebae do not contain hydrogenase, but extracts from cells grown with bacteria do. It is postulated that in bacteria-grown amebae electrons generated at the pyruvate synthase step are utilized anaerobically to produce H2 via the hydrogenase and that the acetyl-CoA is converted to acetate in an energy-conserving step catalyzed by amebal acetyl-CoA synthetase. Aerobically, cells grown under either regimen may utilize the energy-conserving pyruvate-to-acetate pathway since O2 then serves as the ultimate electron acceptor.

Acetate-CoA Ligase↗