Clinical Symptoms Of Experimental Allergic Encephalomyelitis Research Articles

Autologous Haematopoietic Stem Cell Transplantation Followed by Low‐dose Cyclophosphamide Ameliorates the Disease Course and Influences the Microglia Phenotype in Rats With Experimental Allergic Encephalomyelitis

Experimental allergic encephalomyelitis (EAE) is the animal model of multiple sclerosis (MS), the human autoimmune disease, which leads to neurodegeneration. Immune response is developed by autoreactive lymphocytes infiltrating the CNS, but further maintained by resident immune cells, such as microglia. Microglia, until recently was recognized as pro‐inflammatory cells. Lately, it was discovered, that microglia can also differentiate into an anti‐inflammatory phenotype involved in the regression of inflammatory reaction and regenerative processes. Therapy based on the autologous haematopoietic stem cell transplantation (HSCT) was recently approved for treatment of highly‐active or progressive MS. In some regimens the additional conditioning is used after the HSCT to eliminate the autoreactive cells, which may persist after the first dose of chemotherapy.In our experiment, we aimed to investigate the effect of HSCT preceded by high‐dose of cyclophosphamide (CP) on the disease course in rats with evoked EAE, and if the additional, low‐dose of CP following the high‐dose of CP and HSCT may improve the observed effect.Rats with evoked EAE (day 0) were treated with (i) high‐dose (125mg/kg) CP (day +6), followed by HSCT (day +7), or (ii) high‐dose (125mg/kg) CP, followed by HSCT, followed by low‐dose (20mg/kg) CP (day +10, +11). Control animals were (iii) healthy non‐treated and (iv) EAE non‐treated. Clinical symptoms of EAE (0–5 scale) were observed during the disease course and after the resolution of symptoms rats were euthanized. Spinal cords were collected for immunofluorohistochemical analysis to exmine the microglia phenotype in the CNS.Results showed that the applied therapy in the EAE rats, including only the high‐dose CP followed by HSCT did neither improve clinical symptoms observed in the rats nor influenced the microglia phenotype in comparison to the EAE non‐treated animals. However, the additional low‐dose CP after HSCT resulted in the significant reduction of clinical symptoms and increase in the number of anti‐inflammatory microglia in the CNS. There was no effect observed of applied therapies on the numer of pro‐inflammatory microglia.Our results demonstrated, that the appliction of additional low‐dose CP after HSCT led to the increase in the number of anti‐inflammatory microglia in the CNS. This shift into the anti‐inflammatory phenotype might be engaged in the reduction of clinical symptoms in the EAE rats and accentuates the role of microglia in MS pathomechanism.Support or Funding InformationSupported by grant no. 2018/02/X/NZ5/01487 financed by the National Science Centre

Changes in the Qualitative and Quantitative Composition of the Intestinal Microflora in Rats in Experimental Allergic Encephalomyelitis

We report here a study using a model of multiple sclerosis – experimental allergic encephalomyelitis (EAE) – to investigate changes in the qualitative and quantitative composition of the intestinal microbiota in rats with disease symptoms and with a symptom-free course. When clinical symptoms of EAE were apparent, there were changes in the composition of the microbiota of the gastrointestinal tract, with increases in the numbers of Gram-negative opportunistically pathogenic bacteria: Citrobacter spp., Klebsiella spp., and atypical E. coli. Rats without clinical signs of EAE were also found to have increased contents of Faecalibacterium prausnitzii. The significance of complexes changes in the composition of the intestinal microbiota is discussed, as this provides evidence of prolonged persistence of dysbacteriosis in rats on developing EAE.

Cinnamon Ameliorates Experimental Allergic Encephalomyelitis in Mice via Regulatory T Cells: Implications for Multiple Sclerosis Therapy

Upregulation and/or maintenance of regulatory T cells (Tregs) during an autoimmune insult may have therapeutic efficacy in autoimmune diseases. Although several immunomodulatory drugs and molecules are available, most present significant side effects over long-term use. Cinnamon is a commonly used natural spice and flavoring material used for centuries throughout the world. Here, we have explored a novel use of cinnamon powder in protecting Tregs and treating the disease process of experimental allergic encephalomyelitis (EAE), an animal model of MS. Oral feeding of cinnamon (Cinnamonum verum) powder suppresses clinical symptoms of relapsing-remitting EAE in female PLP-TCR transgenic mice and adoptive transfer mouse model. Cinnamon also inhibited clinical symptoms of chronic EAE in male C57/BL6 mice. Dose-dependent study shows that cinnamon powder at a dose of 50 mg/kg body wt/d or higher significantly suppresses clinical symptoms of EAE in mice. Accordingly, oral administration of cinnamon also inhibited perivascular cuffing, maintained the integrity of blood-brain barrier and blood-spinal cord barrier, suppressed inflammation, normalized the expression of myelin genes, and blocked demyelination in the central nervous system of EAE mice. Interestingly, cinnamon treatment upregulated Tregs via reduction of nitric oxide production. Furthermore, we demonstrate that blocking of Tregs by neutralizing antibodies against CD25 abrogates cinnamon-mediated protection of EAE. Taken together, our results suggest that oral administration of cinnamon powder may be beneficial in MS patients and that no other existing anti-MS therapies could be so economical and trouble-free as this approach.

Gemfibrozil Ameliorates Relapsing-Remitting Experimental Autoimmune Encephalomyelitis Independent of Peroxisome Proliferator-Activated Receptor-α

The present study underlines the importance of gemfibrozil, a lipid-lowering drug and an activator of peroxisome proliferator-activated receptor-alpha (PPAR-alpha), in inhibiting the disease process of adoptively transferred experimental allergic encephalomyelitis (EAE), an animal model of relapsing-remitting multiple sclerosis. Clinical symptoms of EAE, infiltration of mononuclear cells, and demyelination were significantly lower in SJL/J female mice receiving gemfibrozil through food chow than those without gemfibrozil. It is noteworthy that the drug was equally effective in treating EAE in PPAR-alpha wild-type as well as knockout mice. Gemfibrozil also inhibited the encephalitogenicity of MBP-primed T cells and switched the immune response from a Th1 to a Th2 profile independent of PPAR-alpha. Gemfibrozil consistently inhibited the expression and DNA-binding activity of T-bet, a key regulator of interferon-gamma (IFN-gamma) expression and stimulated the expression and DNA-binding activity of GATA3, a key regulator of IL-4. Gemfibrozil treatment decreased the number of T-bet-positive T cells and increased the number of GATA3-positive T cells in spleen of donor mice. The histological and immunohistochemical analyses also demonstrate the inhibitory effect of gemfibrozil on the invasion of T-bet-positive T cells into the spinal cord of EAE mice. Furthermore, we demonstrate that the differential effect of gemfibrozil on the expression of T-bet and GATA3 was due to its inhibitory effect on NO production. Although excess NO favored the expression of T-bet, scavenging of NO stimulated the expression of GATA-3. Taken together, our results suggest gemfibrozil, an approved drug for hyperlipidemia in humans, may find further therapeutic use in multiple sclerosis.

1,25 dihydroxyvitamin‐D3 modulates JAK–STAT pathway in IL‐12/IFNγ axis leading to Th1 response in experimental allergic encephalomyelitis

Experimental allergic encephalomyelitis (EAE) is a Th1 cell-mediated autoimmune disease model of multiple sclerosis (MS). Vitamin D deficiency is commonly observed in MS patients and vitamin D supplements reduce the clinical symptoms of EAE and MS. Earlier studies have shown that in vivo treatment with vitamin D analogs ameliorates EAE in association with the inhibition of IL-12 production and Th1 differentiation. The mechanisms in the regulation of Th1 response by vitamin D in EAE/MS are, however, not known. We show that in vivo treatment of C57BL/6 and SJL/J mice (i.p.) with 100 ng of 1,25 dihydroxyvitamin D3, on every other day from Day 0-30, ameliorates EAE in association with the inhibition of IL-12 production and neural antigen-specific Th1 response. In vitro treatment with 1,25(OH)2D3 inhibited IFNgamma-induced tyrosine phosphorylation of STAT1, without affecting JAK2, in EOC-20 microglial cells. Treatment of activated T cells with 1,25(OH)2D3 also inhibited the IL-12-induced tyrosine phosphorylation of JAK2, TYK2, STAT3, and STAT4 in association with a decrease in T cell proliferation in vitro. These findings highlight the fact that vitamin D modulates JAK-STAT signaling pathway in IL-12/IFNgamma axis leading to Th1 differentiation and further suggest its use in the treatment of MS and other Th1 cell-mediated autoimmune diseases.

Presence of nerve growth factor and TrkA expression in the SVZ of EAE rats: evidence for a possible functional significance

Nerve growth factor (NGF) is a well-characterized neurotrophic factor that plays a crucial role during development in the growth, differentiation, and maintenance of brain neurons as well as in the reparative response of the adult brain to neuronal damage. Recent studies have shown that acute axonal loss occurs in multiple sclerosis (MS) and its animal model, experimental allergic encephalomyelitis (EAE), and that NGF suppresses clinical symptoms of EAE in nonhuman primates. Aim of the present study was to investigate the role of NGF in the regenerative response of the adult brain to neuronal damage occurring in EAE. Using EAE rats, we have found that exogenous NGF injection and NGF deprivation (NGF autoimmunization) can act on growth and differentiation of brain precursor cells in the subventricular zone (SVZ) of EAE rats. Moreover, NGF administration in brain of EAE rats stimulates the expression of early neuronal markers on proliferating precursor cells of the SVZ. The data obtained demonstrated that NGF and its antibody affect bromodeoxyuridine (BrdU) incorporation and NGF receptor expression by SVZ progenitor cells in the brain of EAE rats.

Antineuroinflammatory effect of NF-kappaB essential modifier-binding domain peptides in the adoptive transfer model of experimental allergic encephalomyelitis.

It has been shown that peptides corresponding to the NF-kappaB essential modifier-binding domain (NBD) of IkappaB kinase alpha or IkappaB kinase beta specifically inhibit the induction of NF-kappaB activation without inhibiting the basal NF-kappaB activity. The present study demonstrates the effectiveness of NBD peptides in inhibiting the disease process in adoptively transferred experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis. Clinical symptoms of EAE were much lower in mice receiving wild-type (wt)NBD peptides compared with those receiving mutated (m)NBD peptides. Histological and immunocytochemical analysis showed that wtNBD peptides inhibited EAE-induced spinal cord mononuclear cell invasion and normalized p65 (the RelA subunit of NF-kappaB) expression within the spinal cord. Analysis of lymph node cells isolated from donor and recipient mice showed that wtNBD peptides but not mNBD peptides were able to shift the immune response from a Th1 to a Th2 profile. Consistently, wtNBD peptides but not mNBD peptides inhibited the encephalitogenicity of myelin basic protein-specific T cells. Furthermore, i.p. injection of wtNBD peptides but not mNBD peptides was also able to reduce LPS- and IFN-gamma-induced expression of inducible NO synthase, IL-1beta, and TNF-alpha in vivo in the cerebellum. Taken together, our results support the conclusion that NBD peptides are antineuroinflammatory, and that NBD peptides may have therapeutic effect in neuroinflammatory disorders such as multiple sclerosis.

Poster Sessions BP05: Neuroimmunology. Inhibition of adoptive transfer of EAE by nemo‐binding domain (NBD) peptides

Experimental allergic encephalomyelitis (EAE) is the animal model for Multiple Sclerosis (MS), the chronic autoimmune disease of the central nervous system (CNS). Activation of NF‐κB requires the activity of IkB kinase (IKK) complex containing (IKKa and IKKb) and the regulatory protein NEMO (NF‐κB essential modifier). Recently it has been shown that peptides corresponding to the NEMO‐binding domain (NBD) of IKKa or IKKb specifically inhibit the induction of NF‐κB activation without inhibiting the basal NF‐κB activity. The present study underlines the importance of cell‐permeable NBD peptides in inhibiting the disease process of adoptively‐transferred EAE in female SJL/J mice. Immunocytochemical analysis of spinal cords of EAE mice showed that there was marked induction of NF‐κB activation as evidenced by enhanced p65 (the RelA subunit of NF‐κB) expression compared to that of control mice. Double‐labelling analysis of p65 and cell‐specific markers showed that p65 was mainly expressed by astrocytes, microglia and infiltrating macrophages. Next we examined the effect of NBD peptides on the disease process of EAE. Interestingly, clinical symptoms of EAE were much lower in mice receiving wild type NBD peptides. In contrast, mutated NBD peptides had no effect on the clinical symptoms of EAE. Taken together, our results support the conclusion that activation of NF‐κB participates in the disease process of EAE and that inhibitors of NF‐κB activation may ameliorate the neuroinflammatory disease process in MS patients.Acknowledgements: This study was supported by NIH grants (NS39940 and AG19487.

Activation of nuclear factor-kB in the spinal cord of experimental allergic encephalomyelitis

The DNA-binding activity of nuclear factor (NF-kB) was found to be induced in the spinal cord of rats with experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), from the onset of the disease. This activation of NF-kB persisted throughout the disease period and decreased thereafter in the recovery phase. Supershift analysis of NF-kB DNA-binding activity in nuclear extracts of spinal cords showed that RelA/p65 and p50 subunits but not c-Rel/p75, RelB/p68 and p52 subunits were involved in DNA binding. Pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-kB activation, markedly inhibited the in vivo activation of NF-kB in the spinal cord of EAE rats and attenuated the clinical symptoms of EAE. These studies suggest that activation of NF-kB plays an important role in the pathogenesis of EAE and inhibitors of NF-kB activation may have therapeutic importance in MS.

Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis.

Uric acid, the naturally occurring product of purine metabolism, is a strong peroxynitrite scavenger, as demonstrated by the capacity to bind peroxynitrite but not nitric oxide (NO) produced by lipopolysaccharide-stimulated cells of a mouse monocyte line. In this study, we used uric acid to treat experimental allergic encephalomyelitis (EAE) in the PLSJL strain of mice, which develop a chronic form of the disease with remissions and exacerbations. Uric acid administration was found to have strong therapeutic effects in a dose-dependent fashion. A regimen of four daily doses of 500 mg/kg uric acid was required to promote long-term survival regardless of whether treatment was initiated before or after the clinical symptoms of EAE had appeared. The requirement for multiple doses is likely to be caused by the rapid clearance of uric acid in mice which, unlike humans, metabolize uric acid a step further to allantoin. Uric acid treatment also was found to diminish clinical signs of a disease resembling EAE in interferon-gamma receptor knockout mice. A possible association between multiple sclerosis (MS), the disease on which EAE is modeled, and uric acid is supported by the finding that patients with MS have significantly lower levels of serum uric acid than controls. In addition, statistical evaluation of more than 20 million patient records for the incidence of MS and gout (hyperuricemic) revealed that the two diseases are almost mutually exclusive, raising the possibility that hyperuricemia may protect against MS.

2-buten-4-olide (2-B4O) Inhibits Experimental Allergic Encephalomyelitis (EAE) in Lewis Rats

Starvation is well known to induce immune suppression. Moreover, the concentration of 2-B4O, an endogenous sugar acid, is elevated in the circulation during starvation. To determine if these events are related, the influence of 2-B4O on experimental allergic encephalomyelitis (EAE) in Lewis rats, a model of human multiple sclerosis (MS), was studied. EAE, characterized by paralysis of hind legs, was induced by immunization with residues 68 to 84 (MB 68-84) of the guinea pig myelin basic protein (MBP) in complete adjuvant H37Ra. Interestingly, the daily administration of 2-B4O intraperitoneally from the day of MB 68-84 immunization (day 0) to day 20 dramatically suppressed the clinical severity of EAE. The daily administration of 2-B4O intraperitoneally from day 0 to day 7 also markedly reduced the clinical symptoms of EAE. In fact, passively induced EAE, using Con A activated spleen cells from rats immunized with MB 68-84 in H37Ra, was also inhibited by daily administration of 2-B4O. Histological examination confirmed clinical findings and revealed that mononuclear cell infiltration into the central nervous system was significantly inhibited by 2-B4O. To clarify the mechanism(s) responsible for suppression of EAE, the effects of 2-B4O on the immune responses to MB 68-84 were examined. When rats were treated daily with 2-B4O for 15 days after immunization with MB 68-84 in H37Ra, the delayed-type hypersensitivity (DTH) response to MB 68-84 was significantly reduced in 2-B4O treated rats as compared with saline treated rats. The proliferative response to MB 68-84 of spleen cells from 2-B4O treated rats was also significantly lower than that of saline treated rats. Our data demonstrate that 2-B4O has the potential to suppress autoimmune responses in both inductive and effector phases. 2-B4O may have significant potential to treat autoimmune diseases.

Expression of C1q, a subcomponent of the rat complement system, is dramatically enhanced in brains of rats with either Borna disease or experimental allergic encephalomyelitis

In situ hybridization, RT-PCR and Northern blot analysis as well immunohistochemistry were used to examine the expression of C1q, a subcomponent of the rat complement system, in brains of rats infected with Borna disease virus (BDV) and rats afflicted with experimental allergic encephalomyelitis (EAE) induced by the adoptive transfer of myelin basic protein specific T cells. C1q mRNA, which was not detected in normal brain, became clearly detectable using RT-PCR analysis by d14 post infection (p.i.) with BDV. Maximal levels of C1q mRNA were reached 21 days p.i. when inflammatory reactions in the brain were also at a peak. Similarly, C1q mRNA was elevated when the clinical symptoms of EAE became evident 5 days following cell transfer. C1q positive cells, as identified by immunohistology, were preferentially localized in grey and white matter of the hippocampus and basolateral cortex. The C1q positive cells resembled microglial cells in morphology. The correlation of C1q expression with the development of neurological disease as well as the dramatic increase of C1q within brain regions with inflammatory lesions suggest that local biosynthesis of C1q may play a role in the pathogenesis of Borna virus induced and autoimmune encephalomyelitis.

Altered splenic catecholamine concentrations during experimental allergic encephalomyelitis.

Catecholamine concentrations of the spleen were studied with neurochemical techniques in rats injected with myelin basic protein to produce an experimental allergic encephalomyelitis (EAE). Thirteen to 14 days postinoculation the affected rats showed peak clinical signs of weakness, especially in the lower extremities. Resolution of the disease then progressed rapidly with full clinical recovery at day 21. Splenic concentrations of norepinephrine (NE), 3,4-dihydroxyphenylalanine (DOPA), epinephrine (EPI) and 3,4-dihyxroxyphenylethylamine (DA) were determined by HPLC with electrochemical detection. DOPA concentrations were significantly increased (+62%) while DA concentrations were decreased (-29%) in the EAE rats on day 14 postinoculation. NE and EPI concentrations tended to be elevated in the EAE group, but this was not statistically significant. No differences in splenic catecholamines were detected on day 7 and 52 postinoculation between EAE and control animals. These results indicate that changes in the metabolic pathways of splenic catecholamines occur at the peak of the clinical symptoms of EAE; the increase in DOPA and the decrease in DA concentrations suggest that the activity of DOPA-decarboxylase or its co-factor is altered.

The polyclonal antibody responses of lewis rats to the synthetic encephalitogenic neuropeptide S55S (residues 72–84 of guinea pig myelin basic protein) and its analogs

Immunochemical analysis of polyclonal antisera from Lewis rats immunized with peptide analogs and subpeptides of residues 72-84 of guinea pig myelin basic protein (MBP) indicated that there were four main epitopic specificities involved: one represented by residues 76-80, one by residues 72-74, one by 81-84-Gly, and one involving 74-76 in a heteroclitic way even when the immunogen contained a tetraleucine spacer between residues 74 and 75. The affinities were all relatively low, ranging from 3 x 10(4) M-1 to 7.2 x 10(6) M-1, and each affinity population was very restricted with respect to heterogeneity. The results were commensurate with our hypothesis that autoimmune responses to homologous encephalitogenic neuropeptide determinants reflect an evolutionarily imposed degeneration of the overall response, and were also in agreement with our hypothesis that the affinities of autoantibodies against epitopes in the molecular neighborhood of an encephalitogen would be necessarily low. It was also found that peptide 69-81-Gly (S67) in solution would not interact in liquid phase radioimmunoassays with any of the above antibody populations, thus indicating that its preferred conformation did not allow the expression of autoreactive epitopes. There was no evidence that S67 in solution. even in the presence of S53, would express any epitopes reactive with autoantibodies. How this finding for a B cell product correlates with T cell-mediated immunologic responses is not totally understood, but it will be recalled that S67 by itself does not induce T cell-mediated experimental allergic encephalomyelitis (EAE), that S53 (residues 75-84-Gly) induces only clinical symptoms of EAE without attendant pathological disease, but that the two together induce classical EAE.(ABSTRACT TRUNCATED AT 250 WORDS)

Modulation of experimental allergic encephalomyelitis in lewis rats by monoclonal anti-T cell antibodies

The effect of monoclonal antibodies to different T lymphocyte populations of the rat on the induction and the course of experimental allergic encephalomyelitis (EAE) was investigated. EAE was induced by injection of guinea pig spinal cord in adjuvant. Subcutaneous injections of monoclonal antibodies to all peripheral T lymphocytes (W3/13) abrogated or prevented the development of clinical EAE. Similar results were obtained in animals injected with monoclonal antibodies to T helper cells (W3/25) mixed with monoclonal antibodies to T nonhelper cells (OX8). Animals treated with either W3/25 or OX8 developed clinical EAE as the control rats (subcutaneous injected with normal mouse serum). Histological examination after the acute stage revealed no significant differences between rats treated prophylactically with W3/13, W3/25 or OX8 and rats injected with normal mouse serum. Animals treated prophylactically with a mixture of W3/25 and OX8 developed, on the whole, EAE with less histological severity compared to the control animals. Treatment of rats after the onset of the first clinical symptoms of EAE (tail flaccidity) with W3/13 resulted in a less fatal course of the disease. Compared to surviving rats injected with mouse serum (controls) the number of infiltrates were reduced in these rats treated therapeutically.

Immunological cross-reactivity between acid extracts of myelin, liver and neoplastic tissues: studies in immunized guinea-pigs.

Groups of 4 guinea-pigs were immunized with acid extracts prepared from bovine myelin (EF), normal human liver tissue and malignant or benign neoplastic tissues in Freund's complete adjuvant (FCA1. The animals were weighed daily and examined for clinical signs of experimental allergic encephalomyelitis (EAE). All the animals immunized with EF developed clinical symptoms of EAE within 21 days of the initial immunization, whilst some of the animals immunized with certain tumour extracts developed symptoms which closely resembled those of EAE. Control animals immunized with FCA only remained asymptomatic. Cellular immunity to the various extracts in immunized animals was assessed 20 days after immunization by i.d. skin testing, and upon killing at Day 21 with the direct peritoneal-exudate macrophage migration inhibition (MMI) test. Brains and spinal cords were removed at killing, fixed in formalin and processed for histological examination. I.d. skin testing was shown to be most consistent in demonstrating positive delayed hypersensitivity, whilst the MMI test frequently gave negative results in the presence of pronounced skin responses to specific extracts. Thus it was shown that 3/4 animals immunized with basic proteins extracted from an adenocarcinoma of the lung or related hepatic metastases, and 1/2 animals immunized with an extract of a carcinoma of the breast, gave intense erythema and induration responses 5 mm in diameter 24 h after i.d. challenge with EF. No such response was obtained in animals immunized with basic proteins extracted from normal human liver, any of the other neoplastic tissues, or in control animals immunized with FCA only. Examination of brains and spinal cords from animals immunized with EF revealed dense infiltration by mononuclear cells in the ependyma and choroid plexus of levels in the spinal cord. Examination of brains and spinal cords from animals immunized with the lung-tumour extract or related hepatic metastases which showed demonstrable immunological cross-reactivity with EF in immunized animals, revealed a number of inflammatory changes characterized by dense infiltrates of mononuclear cells sub-ependymally, and perivascular cuffing in the cortex. However, no significant lesions were seen in the spinal cords of these animals. Polyacrylamide-gel electrophoresis of the 2 tumour extracts exerting this apparent encephalitogenic effect did not reveal proteins within the mol. wt range of EF. Thus the observed pathological effects and cross-reactivity with EF were probably not due to contamination with nervous-tissue components. It is suggested that these tumour extracts may have contained a component or components other than EF, immunologically cross-reactive with EF, and capable of inducing the observed encephalitis.

Effect of pregnancy on experimental allergic encephalomyelitis in guinea pigs and rats

Pregnancy in guinea pigs and rats exerted a suppressive influence on the development of experimental allergic encephalomyelitis (EAE). Early or late stages in pregnancy had a similar effect in delaying the onset of EAE, a greater delay being observed in pregnant guinea pigs with full term pregnancies. However, the suppressive effect in the majority of animals was only temporary and when they developed the disease the clinical severity was then similar to that in the controls. Clinical symptoms of EAE, in guinea pigs that did not maintain their pregnancy, developed soon after abortion or resorption and these animals deteriorated rapidly. Histologic lesions were markedly enhanced with prominent demyelination in the majority of guinea pigs that were sensitised when pregnant.

Role of peripheral blood lymphocytes in experimental allergic (Pertussis) encephalomyelitis

Peripheral blood lymphocytes of guinea pigs with experimental allergic encephalomyelitis (EAE) induced by a single injection of an oily suspension ofBordetellapertussis cells, when cultured with heterologous brain antigen undergo blast transformation, which is most marked on the 14th–21st day after sensitization. With the development of clinical symptoms of EAE the level of blast transformation of the lymphocytes fell and reached its minimum on the 40th day. It is postulated that this may be connected with the development of transient hypersensitivity and dissemination of sensitized lymphocytes into the CNS, leading to its injury.