Production Of Experimental Allergic Encephalomyelitis Research Articles

Monoclonal antibodies to a TCR idiotope modulate the superantigen-induced responses of encephalitogenic rat T cells.

Superantigens, such as staphylococcal enterotoxins, activate T lymphocytes by linking MHC class II molecules on antigen presenting cells to the V beta element of the TCR. Through this effect on T cells, superantigens may influence the immune response and autoimmune disease. In fact, superantigens may activate or anergize cells involved in the production of experimental allergic encephalomyelitis. Lewis rats recognize an encephalitogenic epitope in myelin basic protein (MBP) residues 68-88 through an MHC class II I-A restricted process using TCR V beta 8.2. The F30 murine mAb reacts with an encephalitogenic idiotope (Id) on the TCR of V beta 8.2+ encephalitogenic Lewis rat T cells. In the present study it was demonstrated that the same mAb anti-Id inhibited the proliferation and IL-2 secretion induced by staphylococcal enterotoxins A, B and E in a V beta 8.2+ encephalitogenic Lewis rat T cell line specific for guinea pig MBP peptide 68-88. The mAb anti-Id did not inhibit the response of control T cells similarly derived but inhibited V beta 8.2- and recognizing MBP peptide 87-99. Control anti-Id failed to inhibit the response of either cell line. These findings imply that the specific antigen and superantigen react with TCR in a manner similar enough to be inhibited by the same anti-Id. The mechanism may involve the induction of anergy by the anti-Id, interference/steric hindrance by the reaction of anti-Id with TCR and possibly a little direct reaction of anti-Id with superantigens. Anti-Id directed immunotherapy may have a role in modulating the damage of inflammatory demyelination induced by both specific antigens and superantigens.

Production of experimental allergic encephalomyelitis with the aid of pertussigen in mouse strains considered genetically resistant

Strains of mice (BALB/c An Bradley/Wehi, C57B1/10J, CBA/ca H Wehi, DBA/2 Wf, A/J Wehi), thought to be genetically resistant to experimental allergic encephalomyelitis (EAE) and known to be resistant to becoming hypersensitive to histamine after administration of pertussis vaccine were tested for their ability to develop EAE when purified pertussigen was included in the immunization. It was found that C57B1/10J, CBA/ca H Wehi, BALB/c An Bradley/Wehi and DBA/2 Wf developed typical signs and histologic evidence of EAE. The A/J Wehi and the B10D2/n Sn (not previously tested) strains developed only mild signs of EAE, while the known susceptible (SJL/J X BALB/c An Bradley/Wehi) F1 hybrids developed severe EAE. Histologic evidence of EAE was lacking in A/J Wehi mice and was minimal in B10D2/n Sn mice. These results suggest that neither the H-2 complex nor the gene controlling susceptibility to sensitization to histamine by administration of pertussigen are wholly responsible for susceptibility to EAE.

Susceptibility of two colonies of Wistar rats to inflammation, with particular reference to delayed hypersensitivity.

Two colonies of Wistar rats were tested for their abilities to produce delayed hypersensitivity reactions and other forms of inflammation. Tuck rats, which respond to dextran with an anaphylactoid reaction, produced delayed reactions to tuberculin protein and to ovalbumin in Freund's incomplete adjuvant. On the other hand, NELP rats which do not respond to dextran also produced delayed reactions to tuberculin protein, but only to ovalbumin when this was contained in Freund's complete adjuvant. Rats of both colonies responded to cotton pellet-induced inflammation, but the adult NELP rats showed resistance both to adjuvant-induced and to collagen-induced arthritis, as well as to the production of experimental allergic encephalomyelitis. NELP rats also showed a much greater reticulo-endothelial system phagocytic activity although antibody titres to sheep red blood cells and the mitogenic activity of concanavalin A and of lipopolysaccharide on spleen cells were similar in the two colonies of rats.

Murine experimental allergic encephalomyelitis.

For approximately fifty years, experimental allergic encephalomyelitis (EAE) has been widely studied. This disease was initially described by Rivers and co-workers (1) as a laboratory model for post-vaccinal encephalomyelitis (PVE). The production of EAE in these initial studies required multiple injections of whole spinal cord homogenate (SCH). After the introduction of Freund’s adjuvant, it became possible to produce EAE in some species with a single injection of SCH (2,3). This facilitated analysis of the responsible encephalitogen which was found to be a component of myelin and subsequently was identified as the myelin basic protein (MBP) (4). Because of pathological similarities between PVE and multiple sclerosis (MS), it has been suspected that similar mechanisms may be operative in the two diseases; however, traditionally EAE has been regarded as an imperfect model for MS because its course is usually monophasic. In 1965, Stone and Lerner (5) described a chronic form of the disease in guinea pigs, and in recent years there has been renewed interest in the investigation of relapsing EAE (REAE) because of its potential relevance to MS (6,7).

Experimental allergic encephalomyelitis induced by basic protein with synthetic adjuvant in comparison with Freund's complete adjuvant: Role of antibodies in correlation with the clinicopathological features

Experimental allergic encephalomyelitis (EAE) was induced in guinea pigs with bovine myelin basic protein (BP) with adjuvant of either synthetic muramyl dipeptide (Mdp) or Mycobacterium tuberculosis (Tbc). The following results were obtained: (1) The body temperature of the animals was studied serially after sensitization and its elevation was shown to be an early sign of EAE. (2) Several animals developed the clinical and histological signs of hyperacute EAE. (3) An optimal combined dosage of BP and adjuvant was found for induction of clinical EAE and for the production of complement fixing (CF) antibodies. (4) Little passive hemagglutinating (PH) antibody was produced by single immunization. These results displayed no essential difference in EAE induced by either adjuvant. (5) Detectable PH antibodies developed later in addition to CF antibodies in a few animals immunized with Tbc adjuvant. These animals were skin-tested to BP, and had recovered from body weight loss or limb weakness. The results suggest that humoral antibodies play a role in modifying the disease process, even if they are not essential in production of EAE.

Experimental allergic encephalomyelitis in cobra venom factor-treated and C4-deficient guinea pigs.

Experimental allergic encephalomyelitis (EAE) was studied in guinea pigs with an inherited deficiency of the fourth component of complement (C4) and in guinea pigs injected with cobra venom factor to deplete the third component and late-acting components of complement. EAE was elicited by immunization with homologous spinal cord or purified basic protein. Administration of cobra factor after the injection of encephalitogenic emulsion delayed the onset and reduced the intensity of the clinical manifestations of EAE. In addition, cobra factor markedly reduced mortality during the sixty days of observation. However, pathological changes of perivascular infiltration and demyelination were similar in cobra factor-treated and untreated animals. Clinical signs of EAE an mortality in C4-deficient guinea pigs were no different from those in normocomplementemic controls. Thus, although activation of the classic complement pathway does not appear to be involved in the production of EAE in guinea pigs, our results suggest a possible role of the alternative complement pathway in the pathogenesis of EAE.

A comparison of autoimmunity and experimental allergic thyroiditis in Strain 2 and Hartley strain guinea pigs

The response of Strain 2 guinea pigs to immunization with thyroid extract in complete adjuvant was compared with the response of the Hartley strain. The Strain 2 did not develop thyroiditis as frequently or in as great a degree as the Hartley strain. This difference in degree of thyroiditis between these two strains occurred consistently even when the animals were immunized with a wide range of doses of thyroid extract and of mycobacteria in adjuvant, and was independent of the strain origin of the antigen used for immunization. Although the Strain 2 made less thyroiditis than the Hartley strain, it made as much agglutinating antibody, and often as much delayed sensitivity as the Hartley strain. The genetic controls regulating autoimminity to the thyroid and production of thyroiditis appear to differ from those regulating production of experimental allergic encephalomyelitis.

Histopathological similarities between scrapie and cuprizone toxicity in mice.

PREVIOUS work with scrapie led us to conclude1 that the transmissible agent was unlikely to be a conventional virus. We have presented evidence2 that the transmissible agent may be, or may be associated with, a small basic protein (polypeptide) of the kind involved in the production of experimental allergic encephalomyelitis, and we have recorded the possible occurrence of the agent in tissues of normal animals3–5. These observations have neither been confirmed nor disproved in other laboratories and various other hypotheses on the nature of scrapie and its transmissible agent remain unproved6–8. The “slow virus” hypothesis still favoured by some9 is now at variance with the impressive experimental evidence from ultraviolet irradiation studies10–13 that the transmissible agent may not contain nucleic acid.

Considerations regarding the possible production of experimental allergic encephalomyelitis in dogs.

Considerations regarding the possible production of experimental allergic encephalomyelitis in dogs.

Pseudomon as Pseudomallei and Pseudomon as Aeruginosa as Adjuvants in the Production of Experimental Allergic Encephalomyelitis

Summary Pseudomonas pseudomallei and Pseudomonas aeruginosa, killed and dried, can replace the killed mycobacteria of complete Freund's adjuvants in the production of experimental allergic encephalomyelitis (EAE) in the guinea pig. Homologous guinea pig spinal cord is the source of the encephalitogenic “antigen” or “hapten.” The disease produced is milder than that produced when mycobacteria are used. P. pseudomallei organisms are also effective mycobacterial substitutes when used with whole bovine spinal cord or lipid extract thereof. Heterologous spinal cord, in this case bovine spinal cord, can cause mild central nervous system lesions of EAE even with incomplete Freund's adjuvants.

Encephalitogenic activity of poly-L-lysine.

IT has recently been reported that a water-soluble protein extracted from brain tissue has encephalitogenic activity1. The method of extraction of this water-soluble protein is very similar to that used by Dounce and Monty for the extraction of histones from rat liver nuclei2. Lederer3 has reported that killed cells of the H 37 RV strain of Mycobacterium tuberculosis can produce allergic encephalomyelitis in rabbits. A basic protein from this same strain has been shown to induce a positive tuberculin reaction4. To determine whether a synthetic basic polypeptide might influence the production of experimental allergic encephalomyelitis we examined the effect of polylysine on this experimental disease in rabbits.

Production of experimental allergic encephalomyelitis in guinea pigs with fractions isolated from bovine spinal cord and killed tubercle bacilli.

Experimental Allergic Encephalomyelitis: Production of Experimental Allergic Encephalomyelitis in Guinea Pigs with Fractions isolated from Bovine Spinal Cord and Killed Tubercle Bacilli

Tubercle bacillus lipopolysaccharide as adjuvant in the production of experimental allergic encephalomyelitis in rabbits.

Tubercle bacillus lipopolysaccharide as adjuvant in the production of experimental allergic encephalomyelitis in rabbits.

A Delayed Chronic Inflammatory Reaction at an Antigen Depot in the Guinea Pig, Effected by Systemic Sensitization

Summary A delayed chronic local inflammatory reaction has been induced in the hind foot of the guinea pig by the simultaneous injection of an antigen-adjuvant emulsion with or without killed tubercle bacilli into the nuchal region, and of the same antigen without adjuvants into the hind foot. Normal rabbit serum, normal horse serum, rabbit anti-rat organ antiserums, therapeutic horse serum preparations, and crystalline chicken ovalbumin served as effective antigens. A chronic arthritic deformity of the foot followed the acute phase. The presence of killed tubercle bacilli in the antigen-adjuvant mixture enhanced the subsequent inflammatory response. It would appear that this phenomenon is an antigen-antibody reaction at a second depot of antigen, in which sensitivity of the tuberculin type may play a significant rôle. It is suggested that the mechanism responsible for the production of experimental allergic encephalomyelitis may be similar in nature to that involved in the local reaction described above.