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Biomedical subjects

D Teitelbaum

Publications and source records attributed to D Teitelbaum.

At least 55 records · Page 3Linked to original sources

The immunologic response in mice unresponsive to experimental allergic encephalomyelitis.

The suppressor cells that are involved in antigen-induced protection against EAE in mice were investigated with respect to their effect on the immune response. The cellular immune response to the basic encephalitogenic protein (BE) and to PPD were studied in mice with either actively induced or adoptively transferred unresponsiveness to EAE. The results demonstrate that the DTH response to BE, as assayed in the radiometric ear skin test, was suppressed in mice protected against EAE. Moreover, the passive transfer of DTH response to BE by effector lymphocytes was also inhibited by the preinjection of suppressor cells. On the other hand, the suppressor cells did not affect the response to PPD in all these experiments. The results indicate that suppressor cells that mediate unresponsiveness to EAE regulate also the cellular immune response to BE in a specific manner. These suppressor cells are probably active both at the induction and the effector phase of the immune response.

Animals

Natural occurrence of thymocytes that react with myelin basic protein.

In adult strain 13 guinea pigs, two lines of evidence show that there are natural autoreactive thymocytes that can react with myelin basic protein (BP) or the encephalitogenic nonapeptide (EP). An autoradiographic binding assay revealed antigen-specific receptors for 125I-BP on thymocytes. A 3H-thymidine antigen-specific proliferation assay demonstrated that normal thymocytes were activated by EP- or BP-pulsed macrophages. Soluble BP suppressed the activation of thymocytes by macrophage-associated BP. The mode of presentation of BP or EP, whether macrophage-associated or soluble, may be critical in maintaining self-tolerance and preventing an autoimmune attack on the central nervous system.

Animals

The effect of Cop 1, a synthetic polypeptide, on chronic relapsing experimental allergic encephalomyelitis in guinea pigs.

Cop 1, a synthetic polypeptide, was evaluated for its effect on a chronic relapsing form of experimental allergic encephalomyelitis (EAE). Pretreatment of juvenile Strain 13 guinea pigs with Cop 1 in incomplete Freund's adjuvant (IFA) which were subsequently challenged with guinea pig spinal cord in complete Freund's adjuvant (CFA) had a marked effect in delaying or preventing the appearance of clinical signs of EAE. Administration of Cop 1 on appearance of clinical signs of EAE prevented progression of the first episode of the disease. Although relapses were not always prevented, they were modified on their duration and intensity both clinically and histologically.

Animals

Effect of cyclophosphamide on suppressor cell activity in mice unresponsive to EAE.

Protection against experimental allergic encephalomyelitis (EAE) was induced in susceptible mice of (SJL/J X BALB/c)F1 hybrid, by injection of either mouse spinal cord homogenate, the small mouse basic protein, or Cop 1 in incomplete Freund's adjuvant, before EAE induction. It was demonstrated that the unresponsiveness induced by the three antigens is mediated by suppressor T cells residing in the spleen cell population and can be adoptively transferred to normal syngeneic recipients. Low dose of cyclophosphamide (20 mg/kg) administered 2 days before the encephalitogenic challenge abrogated the unresponsiveness to EAE and reverted the protected mice sensitive to disease induction. Cyclophosphamide was also active on adoptively transferred unresponsiveness, thus donors that had been treated with cyclophosphamide were unable to further transfer unresponsiveness to EAE. These results indicate the elimination by cyclophosphamide of suppressor cells that interfere with the effector mechanisms leading to EAE.

Animals

The autoimmune features of acute transverse myelopathy.

Lymphocytes from patients with acute transverse myelopathy (ATM) were shown to undergo a specific and significant transformation when cultured in vitro in the presence of either the central nervous myelin basic encephalitogenic protein (BE) or the peripheral nerve myelin P2 protein. A similar pattern of response was demonstrated in acute disseminated encephalomyelitis and in acute myeloradiculitis. Lymphocytes from patients suffering from other autoimmune neurological disorders or other neurological diseases affecting the spinal cord showed no response to there immunologically related antigens, which have previously been found to have the capacity of inducing experimental allergic encephalomyelitis, either alone or with experimental allergic neuritis, when injected into animals. The specific in vitro response to BE and P2 suggests that in vivo sensitization of lymphocytes to such self-antigens occurs in ATM and than a cell-mediated, probably postinfecious autoimmune mechanism may be an important factor in the pathogenesis of the disease.

Acute Disease

Experimental allergic neuritis induced by a basic neuritogenic protein (P1L) of human peripheral nerve origin.

Experimental allergic neuritis (EAN) in the peripheral nervous system, without involvement of the central nervous system, was produced in laboratory animals by the injection of a basic neuritogenic protein, P1L, purified from human peripheral nerves. The animals manifested a positive skin test with P1L, and their lymphocytes were found to be transformed in vitro in the presence of this protein several days before the appearance of the clinical signs. Passive transfer of the disease was performed with lymph node cells from donor guinea pigs immunized with P1L protein. EAN, the experimental model for the human disease Guillaain-Barré syndrome, was shown to be a transient disease and could be suppressed by the administration of hydrocortisone.

Animals

A simple fluorescent method to determine complement-mediated liposome immune lysis.

A simple inexpective method is described to study the kinetics of complement-mediated immune lysis of liposomes containing sheep red blood cell lipid antigens. It is based on the fact that trapping the fluorescent molecule 1-aminonaphthalene-3,6,8-trisulfonate and the dynamic quencher, alpha, alpha'-dipyridinium p-xylene dibromide within the liposome inner volume results in an extinguished fluorescence signal. On addition of helmolysin plus active complement, liposome lysis occurs. The exit of the fluorophore and quencher and their subsequent dilution in the external volume abolishes the quenching, resulting in a high fluorescence signal. The details of the method are described as well as the initial kinetic results.

1-Naphthylamine

Effect of a synthetic polypeptide (COP 1) on patients with multiple sclerosis and with acute disseminated encephalomeylitis. Preliminary report.

Three patients with acute disseminated encephalomyelitis (ADE) and 4 patients in the terminal stages of multiple sclerosis (MS) were subjected to treatment with Cop 1, a synthetic copolymer of amino acids, which had previously been shown to have a beneficial effect in the treatment of experimental allergic encephalomyelitis (EAE). Under the treatment, the ADE patients recovered completely within 3 weeks, but 1 of 2 control cases treated with steroids showed complete recovery as well. The MS patients did not show any significant change in their motor function; however, 2 of them showed some improvement in vision and speech capacity. It is too early to conclude whether this improvement is related to the treatment. No side effect was observed in any of the patients treated with Cop. 1.

Acute Disease

Unprimed spleen cell populations recognize macrophage-bound antigen with opposite net electric charge.

Previous studies have demonstrated an inverse charge relationship between the net electrical charge of antigen and the responding cells. In the present study we attempted to establish whether this phenomenon holds also for the primary recognition phase of cell-mediated immunity, when the involvement of the macrophage in presenting antigen is obligatory. Normal spleen cells were fractionated over negatively and positively charged columns. The fractionated cell populations, as well as the original cells, were sensitized in vitro on macrophage monolayers that were pulsed either with the basic encephalitogenic protein of myelin or with the acidic copolymer poly(Glu50,Tyr50). Cells eluted from glass bead columns(i.e., the more negative cells) could be sensitized only with the basic antigen, while cells eluted from poly(L-lysine)-glass bead columns (i.e., more positive cells) could be sensitized only to the acidic antigen. Thus, in delayed type hypersensitivity the inverse charge relationship prevails also for the primary immunological recognition of antigen bound to macrophages.

Animals