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D Karussis

Publications and source records attributed to D Karussis.

22 records · Page 2Linked to original sources
PubMed1995

Enhancement of GVL effect with rhIL-2 following BMT in a murine model for acute myeloid leukemia in SJL/J mice.

A murine model for acute myeloid leukemia (mAML) was used to study graft-vs.-leukemia (GVL) effects on residual leukemic cells across both major (MHC) and minor histocompatibility antigens (mHA) barriers. In addition, the therapeutic effect of recombinant human interleukin-2 (rhIL-2)-administered postsyngeneic and allogeneic bone marrow transplantation (BMT) was examined. SJL/J mice inoculated with mAML cells were exposed later to total body irradiation (TBI) and transplanted with bone marrow cells (BMC) mixed with spleen cells derived from normal syngeneic (SJL/J), congenic (B10.S), or allogeneic (C57BL/6) donor mice. One-half of the mice in each group received low dose rhIL-2 for 3 days starting 1 day post-BMT. Spleen cells from treated recipients were transferred to secondary naive SJL/J mice for in vivo detection of residual tumor cells. At a tumor load of 10(5) cells per animal, none of the mice rescued with SJL/J or B10.S cells was cured since 100% of secondary recipients developed leukemia. Concomitant treatment of recipients of B10.S cells with rhIL-2 induced GVL effects since none of the secondary recipients developed leukemia after 2 years. All adoptive recipients of mice rescued with C57BL/6 cells remained free of leukemia after 2 years whether or not rhIL-2 was injected. The potency of the GVL effects observed across mHA and MHC were tumor-cell dose dependent since fewer animals inoculated with 10(6) mAML cells were cured. Only marginal GVL effects were noticed following syngeneic BMT and rhIL-2. Our results sustain the importance of the GVL effects in the treatment of myeloid leukemia and demonstrate that immunotherapy with rhIL-2 following BMT can enhance the therapeutic effect induced by the allograft.

Animals↗
PubMed1994

Oral administration of the oxidant-scavenger N-acetyl-L-cysteine inhibits acute experimental autoimmune encephalomyelitis.

The prevention of acute experimental autoimmune encephalomyelitis (EAE) by N-acetyl-L-cysteine (NAC), a potent free radical scavenger, is described. Administrated ad libitum to SJL/J mice at a dosage of 0.2-2 mg/ml in drinking water from the day of the encephalitogenic injection, the agent significantly inhibited the induction of acute EAE. The improvement in clinical condition was dose-dependent. A complete protective effect required administration of the agent at an early stage. Examination of lymphocytes from NAC-treated EAE mice showed that at early stages (days 9 and 15) post encephalitogenic injection the anti-oxidant enhanced the specific lymphocyte proliferative response to the immunizing antigens. Examination of the mitogenic stimulation of lymphocytes from naive animals in the presence of NAC in vitro indicated that the scavenger enhanced the stimulative effect of LPS in a dose-dependent manner. The immunomodulative capacity of the anti-oxidant NAC suggests that free radicals are involved in the pathogenesis of acute EAE.

Acetylcysteine↗
PubMed1992

Delineation of tissue damage mechanisms in experimental autoimmune encephalomyelitis (EAE). I. Cell detachment and lysis induced by encephalitogenic CD4+ T lymphocytes.

Myelin basic protein (MBP) reactive CD4+ T lymphocytes, capable of inducing experimental autoimmune encephalomyelitis (EAE), were examined for their ability to damage target cells of central nervous system (CNS) origin. Damage was assessed by monitoring detachment of adherent astrocytes from substratum and astrocyte lysis. MBP-specific, but non-encephalitogenic CD4+ T cells mediated astrocyte detachment but not lysis. However, encephalitogenic CD4+ T cell lines were more efficient in causing astrocyte detachment and could also cause astrocyte lysis. The detachment and lytic activities of the MBP-reactive T cell lines tested were often independent of the presence of specific antigen, and were not restricted to syngeneic major histocompatibility (MHC) antigens. MBP often augmented the detaching and, if lytic, lytic activities of these T cells. The encephalitogenic CD4+ T cells also detached and lysed allogeneic 'bystander' fibroblasts in the presence of unlabelled syngeneic astrocytes, suggesting the involvement of a soluble mediator(s). Although MBP is essential for the initiation of EAE, the presence of MBP on cells of CNS origin, such as astrocytes and oligodendrocytes, does not appear to be necessary for their damage by MBP-specific CD4+ T cells. Immune CD4+ T cells, which penetrate the CNS, may disorganize brain tissue structure by lysing astrocytes directly and by damaging other brain cells indirectly by soluble mediators. Thus cellular detachment, in addition to cell lysis, mediated by MBP-specific CD4+ cells may contribute to EAE pathogenesis.

Animals↗