Browsing by Author "Mostarica-Stojković, Marija (6701741422)"

T cell subsets in the peripheral blood, draining lymph node (DLN) and spinal cord lesions were analysed after the induction of experimental autoimmune encephalomyelitis (EAE) in susceptible (DA) and relatively resistant (AO) rats. In DA rats, a significantly higher number of CD4+ cells were generated in the DLN, in response to both nervous tissue antigens and complete Freund's adjuvant (CFA), compared to AO rats. In the peripheral blood of DA rats, the percentage as well as absolute number of CD4+ cells increased in the preclinical phase of EAE, but declined as the disease developed. The percentage of CD8+ cells decreased in both these phases of EAE. In resistant AO rats, however, there were no significant changes in the T lymphocyte subset percentage after EAE induction, although the absolute number of peripheral blood CD4+ cells again increased in the preclinical stage of EAE. In the CFA-treated control DA rats, the absolute number of CD4+ cells was increased in the preclinical phase. However, no decline comparable to that seen in diseased animals followed. It is concluded that the generation of CD4+ cells in response to this antigen is strain specific and, since the cells are released into the circulation, will affect the balance between the T cell subsets in the peripheral blood during the development of EAE. © 1990.

T cell subsets in the peripheral blood, draining lymph node (DLN) and spinal cord lesions were analysed after the induction of experimental autoimmune encephalomyelitis (EAE) in susceptible (DA) and relatively resistant (AO) rats. In DA rats, a significantly higher number of CD4+ cells were generated in the DLN, in response to both nervous tissue antigens and complete Freund's adjuvant (CFA), compared to AO rats. In the peripheral blood of DA rats, the percentage as well as absolute number of CD4+ cells increased in the preclinical phase of EAE, but declined as the disease developed. The percentage of CD8+ cells decreased in both these phases of EAE. In resistant AO rats, however, there were no significant changes in the T lymphocyte subset percentage after EAE induction, although the absolute number of peripheral blood CD4+ cells again increased in the preclinical stage of EAE. In the CFA-treated control DA rats, the absolute number of CD4+ cells was increased in the preclinical phase. However, no decline comparable to that seen in diseased animals followed. It is concluded that the generation of CD4+ cells in response to this antigen is strain specific and, since the cells are released into the circulation, will affect the balance between the T cell subsets in the peripheral blood during the development of EAE. © 1990.

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis, a chronic inflammatory and demyelinating disease of the CNS. Albino Oxford (AO) rats are resistant to the induction of EAE, while the disease can be readily induced in Dark Agouti (DA) rats. Here we investigated a potential contribution of the CNS milieu in the limitation of the encephalitogenic autoimmune response. EAE was induced by immunization of the respective rat strains with spinal cord homogenate emulsified in complete Freund's adjuvant. AO rats did not exhibit clinical signs after immunization while DA rats developed severe neurologic deficits. Infiltration of immune cells into spinal cords (SC) was evident in both strains 12-14 days after the immunization. EAE lesions of AO rats contained substantially lower numbers of CD4+ T cells and CD11b+ cells compared to those in DA rats. This went together with lower levels of interferon (IFN)-γ and interleukin (IL)-17 in the cells isolated from SC. We found a dramatic increase of CXCL12 expression in SC tissue and microvessels of AO rats, whereas DA rats markedly decreased the expression of this chemokine within their CNS. Administration of the CXCL12 antagonist AMD3100 to a substrain of AO rats that developed a weak EAE led to earlier onset and exacerbation of the disease. These results suggest a role of CXCL12 in down-regulating autoimmune processes in AO rats during EAE. Therapeutic modulation of CXCL12 could be a promising strategy for the treatment of CNS autoimmunity. © 2011 Elsevier GmbH.

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis, a chronic inflammatory and demyelinating disease of the CNS. Albino Oxford (AO) rats are resistant to the induction of EAE, while the disease can be readily induced in Dark Agouti (DA) rats. Here we investigated a potential contribution of the CNS milieu in the limitation of the encephalitogenic autoimmune response. EAE was induced by immunization of the respective rat strains with spinal cord homogenate emulsified in complete Freund's adjuvant. AO rats did not exhibit clinical signs after immunization while DA rats developed severe neurologic deficits. Infiltration of immune cells into spinal cords (SC) was evident in both strains 12-14 days after the immunization. EAE lesions of AO rats contained substantially lower numbers of CD4+ T cells and CD11b+ cells compared to those in DA rats. This went together with lower levels of interferon (IFN)-γ and interleukin (IL)-17 in the cells isolated from SC. We found a dramatic increase of CXCL12 expression in SC tissue and microvessels of AO rats, whereas DA rats markedly decreased the expression of this chemokine within their CNS. Administration of the CXCL12 antagonist AMD3100 to a substrain of AO rats that developed a weak EAE led to earlier onset and exacerbation of the disease. These results suggest a role of CXCL12 in down-regulating autoimmune processes in AO rats during EAE. Therapeutic modulation of CXCL12 could be a promising strategy for the treatment of CNS autoimmunity. © 2011 Elsevier GmbH.

Dark August rats exhibit clinically and histologically verified experimental allergic encephalomyelitis (EAE) when immunized with appropriate antigen (nervous tissue, myelin basic protein) emulsified in complete Freund’s adjuvant (CFA). We provide evidence that 6, 6′-trechalose dymicolate (TDM) incorporated in incomplete Freund’s adjuvant replaces CFA in EAE induction. The animals that recovered from EAE were resistant to the reinduction of the disease irrespectively whether Mycobacterium tuberculosis or TDM was used as an adjuvant. Finally, pretreatment with CFA alone was sufficient for prevention of disease elicited by challenge with encephalitogen + CFA. However, TDM, despite its adjuvant capacity when applied prior to the induction of the disease with encephalitogen + CFA, did not exhibit any protective effect. Thus, our study implicates that adjuvant and suppressive capacities of M. Tuberculosis may be related to the different determinants of the microorganisms, TDM possessing the adjuvanticity only. © 1988 S. Karger AG, Basel.

Dark August rats exhibit clinically and histologically verified experimental allergic encephalomyelitis (EAE) when immunized with appropriate antigen (nervous tissue, myelin basic protein) emulsified in complete Freund’s adjuvant (CFA). We provide evidence that 6, 6′-trechalose dymicolate (TDM) incorporated in incomplete Freund’s adjuvant replaces CFA in EAE induction. The animals that recovered from EAE were resistant to the reinduction of the disease irrespectively whether Mycobacterium tuberculosis or TDM was used as an adjuvant. Finally, pretreatment with CFA alone was sufficient for prevention of disease elicited by challenge with encephalitogen + CFA. However, TDM, despite its adjuvant capacity when applied prior to the induction of the disease with encephalitogen + CFA, did not exhibit any protective effect. Thus, our study implicates that adjuvant and suppressive capacities of M. Tuberculosis may be related to the different determinants of the microorganisms, TDM possessing the adjuvanticity only. © 1988 S. Karger AG, Basel.

A myelin basic protein (MBP)-specific T cell line derived from F1 hybrids between experimental allergic encephalomyelitis (EAE)-susceptible DA (RT1av1) strain and EAE-resistant AO (RT1u) strain was capable of inducing clinical EAE in F1 hybrids and DA, but not in AO rats. In vitro restimulation with MBP presented by AO antigen-presenting cells (APC) resulted in the generation of a MBP-specific subline restricted by RT1u MHC products which induced clinical EAE in F1 hybrids but not in the AO parental strain. Deletion of hosts' leukocytes using sublethal irradiation and cytotoxic drugs did not abrogate the resistance of AO rats, which argues against the involvement of hosts' lymphoid cells in the regulation of autoagression. Thus, mechanism(s) regulating the activity of autoagressive T cells on functional elements in the target tissue might be responsible for differences in susceptibility to EAE. © 1992.

A myelin basic protein (MBP)-specific T cell line derived from F1 hybrids between experimental allergic encephalomyelitis (EAE)-susceptible DA (RT1av1) strain and EAE-resistant AO (RT1u) strain was capable of inducing clinical EAE in F1 hybrids and DA, but not in AO rats. In vitro restimulation with MBP presented by AO antigen-presenting cells (APC) resulted in the generation of a MBP-specific subline restricted by RT1u MHC products which induced clinical EAE in F1 hybrids but not in the AO parental strain. Deletion of hosts' leukocytes using sublethal irradiation and cytotoxic drugs did not abrogate the resistance of AO rats, which argues against the involvement of hosts' lymphoid cells in the regulation of autoagression. Thus, mechanism(s) regulating the activity of autoagressive T cells on functional elements in the target tissue might be responsible for differences in susceptibility to EAE. © 1992.

Considering the role of pleiotropic interleukin-1 (IL-1) in inflammation and autoimmunity, studies were designed to examine whether specific blockade of IL-1 may influence these processes in the CNS. Although the role of CD4+ T cells in eliciting clinical signs of experimental autoimmune encephalomyelitis (EAE) has been unequivocally demonstrated, the exact mechanism by which encephalitogenic cells initiate disease process and bring about clinical signs still remains to be defined. We have evaluated the effect of human recombinant interleukin-1 receptor antagonist (IL-1Ra) in vivo on the course of actively induced EAE in highly susceptible Dark Agouti (DA) rats. The rats which were treated during the induction phase of disease (days 0-6) with IL-1Ra (350 μg/rat/day) developed milder signs of EAE, when compared to saline-treated control animals immunized with encephalitogen, which developed severe single episode disease. The transfer of lymph node cells (LNC) isolated from MBP-primed DA rats and stimulated in vitro with MBP and ConA to naive syngeneic animals resulted in the development of EAE in all recipients. However, rats injected with LNC that have been stimulated in vitro in the presence of IL-1Ra (10 μg/ml) developed significantly milder disease. Diminished encephalitogenic capacity of LNC correlated with lower proliferative response to antigen and mitogen and decreased expression of IL- 2 receptors. These data provide further evidence that IL-1 is an important factor for activation of EAE inducing T lymphocytes.

Considering the role of pleiotropic interleukin-1 (IL-1) in inflammation and autoimmunity, studies were designed to examine whether specific blockade of IL-1 may influence these processes in the CNS. Although the role of CD4+ T cells in eliciting clinical signs of experimental autoimmune encephalomyelitis (EAE) has been unequivocally demonstrated, the exact mechanism by which encephalitogenic cells initiate disease process and bring about clinical signs still remains to be defined. We have evaluated the effect of human recombinant interleukin-1 receptor antagonist (IL-1Ra) in vivo on the course of actively induced EAE in highly susceptible Dark Agouti (DA) rats. The rats which were treated during the induction phase of disease (days 0-6) with IL-1Ra (350 μg/rat/day) developed milder signs of EAE, when compared to saline-treated control animals immunized with encephalitogen, which developed severe single episode disease. The transfer of lymph node cells (LNC) isolated from MBP-primed DA rats and stimulated in vitro with MBP and ConA to naive syngeneic animals resulted in the development of EAE in all recipients. However, rats injected with LNC that have been stimulated in vitro in the presence of IL-1Ra (10 μg/ml) developed significantly milder disease. Diminished encephalitogenic capacity of LNC correlated with lower proliferative response to antigen and mitogen and decreased expression of IL- 2 receptors. These data provide further evidence that IL-1 is an important factor for activation of EAE inducing T lymphocytes.

Concentrations of interleukin (IL)-12 and tumor necrosis factor-α (TNF-α) in cerebrospinal fluid (CSF) were measured in patients with multiple sclerosis (MS) and control patients with non-inflammatory neurological diseases (NIND) by an enzyme-linked immunosorbent assay. TNF-α was detectable in the CSF of 60% of the patients with active MS, none of those with inactive MS and 29% of patients with NIND. CSF concentrations of TNF-α correlated with the degree of disability in MS patients (P<0.05). Detectable levels of IL-12 were found in 10% of the MS CSF samples and 18% of NIND CSF samples. There was a significant relationship between CSF concentrations of IL-12 and those of TNF-α in MS patients (P<0.05); no relationship was observed between the presence of IL-12 and disease activity or severity. These findings further stress the involvement of T helper 1 type-response within the central nervous system in MS.

Concentrations of interleukin (IL)-12 and tumor necrosis factor-α (TNF-α) in cerebrospinal fluid (CSF) were measured in patients with multiple sclerosis (MS) and control patients with non-inflammatory neurological diseases (NIND) by an enzyme-linked immunosorbent assay. TNF-α was detectable in the CSF of 60% of the patients with active MS, none of those with inactive MS and 29% of patients with NIND. CSF concentrations of TNF-α correlated with the degree of disability in MS patients (P<0.05). Detectable levels of IL-12 were found in 10% of the MS CSF samples and 18% of NIND CSF samples. There was a significant relationship between CSF concentrations of IL-12 and those of TNF-α in MS patients (P<0.05); no relationship was observed between the presence of IL-12 and disease activity or severity. These findings further stress the involvement of T helper 1 type-response within the central nervous system in MS.

Background/Aim: The aim of this study was to compare plasma and urine transforming growth factor-β1 (TGF-β1) levels in patients with different stages of Balkan endemic nephropathy (BEN) with those in patients with primary glomerulonephritis (GN) and healthy controls. Methods: The study involved 47 patients with BEN (30 with manifest BEN and 17 in the early stage of BEN), 12 patients with GN and 10 healthy controls. Plasma and urine TGF-β1 was assayed by enzyme-linked immunosorbent assay. Results: The median plasma TGF-β1 levels differed nonsignificantly between the groups (4,908-6,442 pg/ml), but individual plasma TGF-β1 levels in BEN patients exhibited the highest dispersion. Median urinary TGF-β1 excretion (pg/mg creatinine) was significantly higher in patient groups (manifest BEN: 203, early-stage BEN: 341, GN: 775) than in healthy controls (42). No correlation was found between plasma and urine TGF-β1 levels or between plasma TGF- β1 levels and creatinine clearance for any of the examined groups. Conclusion: Plasma TGF-β1 levels in BEN patients extended over the widest range, but no significant differences were found between the median values for the groups. Median urinary TGF-β1 excretion was significantly higher in patients with BEN and GN than in healthy controls. Copyright © 2009 S. Karger AG.