Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spleen cells from myelin basic protein (BP)-sensitized donor rats appear to be incapable of adoptively transferring experimental allergic encephalomyelitis (EAE) directly to normal recipients. It has been reported that in vitro incubation with concanavalin A (Con A) activates rat spleen cells so that they are capable of transferring EAE. We report here that incubation with specific antigen, BP, also permits transfer of disease with spleen cells. Data are presented in which activation of EAE spleen cells by Con A is compared with activation by BP. Cellular proliferation does not appear to be necessary for in vitro activation with specific antigen.
 ...
PMID:Adoptive transfer of experimental allergic encephalomyelitis: incubation of rat spleen cells with specific antigen. 8 24

Adoptive transfer of experimental allergic encephalomyelitis (EAE) with splenic lymphocytes from Lewis rats sensitized to myelin basic protein (BP) was potentiated by incubation of the cells in vitro with concanavalin A (Con A). Spleen cells of donors which had recovered from EAE also transferred the disease readily after activation by this procedure. In contrast, the transfer of activity of lymph node cells was not altered. We conclude that during the course of EAE a population of T cells with immunologic memory for BP is generated and persists in the spleen. Incubation with Con A activates these cells and results in marked enhancement of their ability to transfer the disease.
 ...
PMID:Experimental allergic encephalomyelitis: enhancement of cell-mediated transfer by concanavalin A. 30 72

Chronic-relapsing experimental allergic encephalomyelitis (CR-EAE) in the Lewis rat, induced by the injection of spinal cord tissue in complete Freund's adjuvant (SC/CFA), was studied in vivo by treatment with liposomes containing central nervous tissue antigens, and in vitro by lymphocyte proliferation assays. Intracardiac administration of myelin basic protein (MBP) liposomes, galactocerebroside (GC) liposomes, or MBP + GC liposomes substantially reduced the clinical severity and/or delayed the onset of the initial phase of disease. Liposomes prepared from whole myelin provided even greater protection, and were effective at suppressing both the first disease episode and the relapses. These results indicate that while GC and MBP may play significant roles in the development of CR-EAE in the Lewis rat, immune responses to other antigens are probably also involved. Splenic and lymph node lymphocytes from MBP-GC liposome-treated rats, and splenic lymphocytes from cytochrome-GC (CYT-GC) liposome-treated rats, showed drastically reduced abilities to proliferate in response to MBP in culture. Spleen cells from both the MBP-GC- and CYT-GC-liposome-treated donors were able to actively suppress antigen-induced proliferation of MBP-primed lymphocytes. These findings suggest participation of both clonal anergy, and active suppressor cells in the liposome-mediated suppression of CR-EAE in the Lewis rat.
 ...
PMID:Treatment of spinal cord-induced experimental allergic encephalomyelitis in the Lewis rat with liposomes presenting central nervous system antigens. 169 33

Lewis rats immunized with myelin basic protein (MBP) in Freund's complete adjuvant (FCA) suffer from a single episode of paralysis from which they recover spontaneously. Subsequent to recovery, further episodes of paralysis cannot normally be induced by reimmunization with MBP in FCA. It is well established that serum, obtained from rats in the refractory state, can suppress the induction of experimental allergic encephalomyelitis (EAE) when given to animals from the time of immunization with MBP in FCA. Here it is shown that treatment with some such sera from Day 7 after immunization also suppressed the disease. However, not all convalescent sera were suppressive, indicating that rats immunized with MBP in FCA could become refractory to EAE without assayable levels of suppressive activity in their sera. In the context of this result it was notable that a correlation was found between the level of antibody specific for the encephalitogenic peptide in sera and the ability to suppress EAE. An inverse relationship was also shown between the amount of anti-encephalitogenic peptide antibody produced after immunization and the severity of EAE induced. Spleen cells from animals treated with Lewis anti-MBP serum after immunization with MBP in FCA could be activated to transfer EAE by in vitro culture with MBP despite the absence of any clinical signs in the donor animals, i.e. the serum inhibited the expansion or differentiation of these cells rather than preventing their priming or bringing about clonal deletion.
 ...
PMID:The role of serum factors in the suppression of experimental allergic encephalomyelitis: evidence for immunoregulation by antibody to the encephalitogenic peptide. 169 65

Immunization protocols that induce high levels of delayed-type hypersensitivity are often associated with low levels of antibody production, whereas alternative immunization strategies can produce the opposite effect. This reciprocal relationship appears to depend, at least in part, on the fact that T cell-derived lymphokines that are predominantly involved in one type of response inhibit the development of those T cells that promote the alternative one. Such a regulatory mechanism is likely to be bistable in that whenever one form of response is established, spontaneous development of the alternative one will be inhibited. We have applied this concept to the control of a cell-mediated autoimmune disease in rats. By covalently linking the autoantigen to anti-IgD antibody, we have targeted it to B cells for presentation to antigen-specific T cells. This form of presentation favors antibody production and may be expected to antagonize the cell-mediated disease-inducing response to the same antigen. To test this hypothesis, use was made of the fact that experimental allergic encephalomyelitis (EAE), when induced with the encephalitogenic peptide of guinea pig myelin basic protein, is purely a cell-mediated disease. The experiments show that Lewis rats, immunized with the peptide in its encephalitogenic form, were protected from disease when simultaneously injected with the peptide coupled to anti-IgD monoclonal antibodies. Control experiments showed that neither peptide nor anti-IgD alone were protective, and the peptide covalently coupled to irrelevant antibodies also failed to protect. Spleen cells from animals protected from disease by the anti-IgD-peptide conjugate, when activated in vitro with the encephalitogen, were able to transfer EAE to naive recipients. The results demonstrate that a cell-mediated immune response can be controlled by appropriate targeting of the specific antigen without inducing T cell anergy and suggest a potential strategy for preventing autoimmune diseases that are essentially cell-mediated in type.
 ...
PMID:Targeting autoantigen to B cells prevents the induction of a cell-mediated autoimmune disease in rats. 174 Jun 60

Spleen cells (SC) from tumor-bearing mice and mice immunized with porcine myelin basic protein (MBP) reacted in vitro in E-rosette augmentation assays with MBP and certain of its constituent peptides. Peptides 1-115, 43-169, 64-83, 113-121, and 153-161 reacted significantly with both types of SC, while peptide 1-19 reacted only with SC from MBP-immunized mice. The phenomenon of specific inhibition of peptide reactivity by a moderate excess of a related protein was used to identify peptides as accessible epitopes of that protein. Peptide 113-121 was specifically inhibited by excess MBP when reacted with both types of SC, whereas peptide 64-83 was inhibited by excess MBP only when reacted with SC from MBP-immunized mice. These reactions suggest that the immunizing antigen in tumor-bearing mice is related to MBP but differs in epitopes associated with peptides 1-19 and 64-83.
 ...
PMID:Cell-mediated immunoreactivity of tumor-bearing mice with myelin basic protein and related peptides. 242 11

Spleen cells from rats that have recovered from experimental autoimmune encephalomyelitis (EAE) suppress the production of IFN-gamma by effector T cells of EAE in an Ag-specific manner. These postrecovery suppressor cells also inhibit EAE in vivo. Fractionation of the postrecovery suppressor spleen cells on nylon wool and OX-8 coated plates yields a nylon wool-adherent CD4+ suppressor cell population that, when cocultured with effector T cells, suppresses IFN-gamma production by these effector cells. In contrast, the nylon wool-adherent, CD4+ postrecovery suppressor cell population fails to inhibit the production of IL-2 by the effector T cells. In further experiments, the effector T cell population was depleted of CD8+ cells and cocultured with the nylon wool-adherent, CD4+ postrecovery suppressor cells, and the supernatants were assayed for IFN-gamma and IL-2. IFN-gamma production was inhibited in these cultures but IL-2 production was not inhibited. Irradiated effector T cells were cocultured with CD4+ postrecovery suppressor cells, without myelin basic protein, in an effort to determine whether the mechanism of differential lymphokine suppression involved an anti-idiotypic response against effector T cells. No IL-2 was produced, indicating that there was no CD4+ suppressor cell mediated anti-idiotypic response against effector T cells. These studies suggest that the suppressor cell is a nylon wool adherent, CD4+ T cell that functions to down-regulate EAE effector T cells by differential inhibition of lymphokine production.
 ...
PMID:CD4+ suppressor cells differentially affect the production of IFN-gamma by effector cells of experimental autoimmune encephalomyelitis. 257 35

Previous work from this laboratory has shown that resistance to acute experimental autoimmune encephalomyelitis (EAE) correlates with disease-specific, antigen-induced suppression of blastogenesis in vitro. We now report that this suppression in vitro also occurs during remissions in animals with chronic-relapsing EAE. Hartley strain guinea pigs were injected with an homogenate of guinea pig spinal cord in complete Freund's adjuvant (CFA) to induce EAE or, for control purposes, with CFA alone. Animals injected with spinal cord homogenate developed EAE. Susceptible animals displayed up to 3 exacerbations over 4-5 months. Spleen cells and nervous tissue were sampled from different animals during and after each exacerbation. Gross examination of nervous tissue revealed plaques that at the light microscope level were characteristic of chronic-relapsing EAE. Lymphocyte transformation assays using the T-cell mitogen concanavalin A (Con A), guinea pig myelin basic protein (BP), the purified protein derivative of M. tuberculosis (PPD) and histone proteins were conducted. Results of these assays showed that in spleen cells from animals sampled during remissions, BP suppressed the Con A response. Similar suppression was not observed with spleen cells from animals in exacerbation. This suppression depended upon the presence of adherent cells. Neither PPD nor histone proteins suppressed the Con A response. Thus, an immunologic mechanism, similar to that observed in Hartley guinea pigs resistant to acute EAE, is also found during remissions in the chronic-relapsing form of this disease suggesting that both resistance and remission are mediated by an antigen-induced suppressor mechanism.
 ...
PMID:Chronic-relapsing experimental autoimmune encephalomyelitis. Myelin basic protein induces suppression of blastogenesis during remissions but not during exacerbations. 257 93

We utilized a system of sequential in vitro cell culture and adoptive transfer to investigate the sequence of events which lead to the activation of effector cells responsible for the induction of experimental autoimmune encephalomyelitis (EAE) in Lewis rats. This procedure involves only naive (nonimmune) rats, and eliminates the requirement for adjuvants. Spleen cells (SpC) from naive donors were sensitized in vitro to myelin basic protein (BP), then transferred to intermediate (primary) hosts. Although these recipients did not develop EAE, they were primed for disease because they exhibited accelerated onset of active EAE when challenged with BP in adjuvant. Moreover, SpC from nonchallenged primary recipients transferred EAE to secondary recipients subsequent to in vitro exposure to antigen. The cells from the naive cultures which primed the intermediate recipients were radioresistant (1500 R); other studies have indicated that these are macrophages. In contrast, the cells which transferred EAE to the secondary recipients were radiation-sensitive T lymphoblasts. The finding that these cells also elicit disease in lethally irradiated (850 R) secondary recipients suggests that the transferred cells either are the actual effector cells of EAE or induce disease in collaboration only with radioresistant host cells.
 ...
PMID:Autoimmune effector cells. VIII. Cellular requirements for the induction of autoreactive T cells of experimental allergic encephalomyelitis in nonimmune rats. 348 50

Clinical resistance to the induction of experimental allergic encephalomyelitis was observed in a closed colony of Lewis (designated Le-R) rats. Disease susceptibility in randomly bred animals appeared to increase with increasing age. In the small group of young Le-R rats, which were susceptible, disease onset was delayed, severity of symptoms was reduced, and duration of clinical signs was abbreviated compared to conventional Lewis rats. The severity of histologic neural tissue lesions correlated with clinical observations. Breeding experiments indicated that most Le-R rats were resistant to disease induction regardless of whether their ancestors had been selected for susceptibility or resistance. The F3 generation of resistant lineage was uniformly resistant at all ages tested. Virtually all (Lewis X Le-R)F1 rats of either sex were resistant when challenged at 7-8 wk of age indicating that resistance was a dominant autosomal trait. Approximately half of (F1 X Lewis) backcross rats developed paralytic EAE whereas one-fourth were entirely resistant, suggesting that disease resistance may be mediated by one or two genes. Le-R rats shared at least some of the Lewis rat major histocompatibility antigens. Resistance apparently did not reflect a nonspecific impairment of cellular immune responsiveness. Le-R rats, which had been challenged with myelin basic protein, developed antigen-reactive cells specific for basic protein or its encephalitogenic fragment. Spleen cells obtained from basic protein-sensitized Le-R rats did not adoptively transfer disease into Lewis rats. In contrast, spleen cells obtained from basic protein-sensitized Lewis rats readily transferred disease into both Lewis and Le-R recipients. These data suggest that disease resistance may be a result of an immunologic deficit (or suppressor cell activity) expressed during the differentiation of antigen-reactive cells into disease-inducing effector cells.
 ...
PMID:Genetic resistance to the induction of experimental allergic encephalomyelitis in Lewis rats. I. Genetic analysis of an apparent mutant strain with phenotypic resistance to experimental allergic encephalomyelitis. 616 Dec 6


1 2 Next >>