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Proposed role of apoptosis in the immunopathology and immunoregulation of experimental autoimmune encephalomyelitis
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receptor (TCR). Based on this finding, vaccination with synthetic peptides corresponding to the TCR V region sequence has been proposed to prevent the development of experimental autoimmune encephalomyelitis (EAE). However, there are some controversies with regard to effectiveness of the therapy. By using various immunization protocols, we examined whether or not vaccination with the TCR peptide (V/38 39-59) protected Lewis rats from EAE. Consequently, we found that the vaccination was effective only when the peptide was immunized with mycobacteria-enriched complete adjuvants, enough to generate T cells reactive with the TCR peptide. Immunohistochemical staining and flow cytometry using anti-TCR peptide antibody revealed that there were virtually no positive cells in lymphoid organs and E A E lesions in the spinal cord, suggesting that this peptide sequence in the TCR molecule is cryptic. Therefore, the frequency of T C R peptide-reactive T cells might be very low and strong immunization is necessary for the induction of overt T cell response.
Modulation of phagocytosis in peripheral monocytes and alveolar macrophages from normal subjects and chronic bronchitis patients by synthetic bombesin F. Meloni, P. Ballabio, P. Mangiarotti, L. Bianchi and G. Gialdroni Grassi
Chair of Chemotherapy and Institute of Respiratory Diseases, University of Pavia, Pavia, Italy Bombesin (BN)-related peptides (BRP) are present in humans in many body systems with a variety of biological activities. They exert trophic action in the lung during foetal life and are mitogenic for normal bronchial epithelial cells, and pulmonary fibroblasts. Increased levels of BRP have been described in the lung of cigarette smokers and in smoking related diseases. BRP have also been involved in the network of neuroimmune interactions having shown to be chemotactic for human monocytes (Mo) and to modulate phagocytic function of murine peritoneal macrophages. Wiedermann and coll. showed that human Mo and guinea pig alveolar macrophages (AM) contain appreciable amounts of BRP. We also detected higher BRP levels in Mo and AM of chronic bronchitis (CB) patients compared to normals. Aim of this study is to assess the influence of BN on the in vitro phagocytosis of Mo and AM from a group of CB patients (n = 22) and a group of normal subjects (n = 21). Phagocytosis (calculated as phagocytosis index = Phi and phagocytosis frequency = PhF) was performed on Mo and AM preincubated for 60'_+ BN (concentrations range: 1010 Mol). BN pretreatment significantly enhanced the Phi of Mo and AM in both groups of subjects in a dose-dependent manner. In the CB group, BN activity
was more pronounced: mean Phi value of Mo was 1.88_+ 0.46 in control cells and 3.067_+ 0.55 in cells pretreated with BN 10 Mol. Our preliminary data, showing that BN can interfere in some phagocytic functions, may imply a potential immunomodulating role for BRP in lung response to some pathological noxae.
Proposed role of apoptosis in the immunopathology and immunoregulation of experimental autoimmune encephalomyelitis M.P. Pender, P.A. McCombe, G. Yoong and K.B. Nguyen
Neuroimmunology Research Unit, Department of Medicine, The University of Queensland, Royal Brisbane Hospital, Brisbane, Australia We have recently reported that apoptosis (programmed cell death) occurs in the nervous system in experimental autoimmune encephalomyelitis (EAE) induced by inoculation with myelin basic protein (MBP) in the Lewis rat (J. Neurol. Sci. (1991) 104, 81-87). Here we show, using immunocytochemistry, that about half of the apoptotic cells in the spinal cord of Lewis rats with acute MBP-EAE are a/~ T Iymphocytes. Apoptosis has recently been shown to provide a mechanism of thymic and peripheral tolerance through the clonal elimination of immature and mature T cells. We, therefore, hypothesize that apoptosis of MBPspecific T cells in the nervous system contributes to the subsidence of inflammation and, if ongoing, to the acquisition of tolerance after an attack of acute EAE. Furthermore, some of the apoptotic cells in the spinal cord are likely to be oligodendrocytes. As apoptosis is a mechanism by which cytotoxic T cells kill their targets, we also propose that oligodendrocyte apoptosis occurs in E A E as a result of MBP-specific T cell cytotoxicity and that this is an important mechanism of demyelination in EAE.
CD4 + T cells and cytokines in murine EAE Toufic Renno, Rana Zeine, Marc Girard and Trevor Owens
McGill University, Montreal Neurological Institute, Montreal, Quebec, Canada In experimental allergic encephalomyelitis (EAE), CD4 + T cells infiltrate the CNS to induce disease. We have examined cytokine production by infiltrating CD4 + T cells in S J L / J mice with spinal cord or MBP-induced EAE. PCR amplification of R N A from whole CNS showed a strong increase in levels of m R N A for CD3, IL-2, IFN-y and TNF-a over barely detectable levels in unimmunized mice. Immunoperoxi-
receptor (TCR). Based on this finding, vaccination with synthetic peptides corresponding to the TCR V region sequence has been proposed to prevent the development of experimental autoimmune encephalomyelitis (EAE). However, there are some controversies with regard to effectiveness of the therapy. By using various immunization protocols, we examined whether or not vaccination with the TCR peptide (V/38 39-59) protected Lewis rats from EAE. Consequently, we found that the vaccination was effective only when the peptide was immunized with mycobacteria-enriched complete adjuvants, enough to generate T cells reactive with the TCR peptide. Immunohistochemical staining and flow cytometry using anti-TCR peptide antibody revealed that there were virtually no positive cells in lymphoid organs and E A E lesions in the spinal cord, suggesting that this peptide sequence in the TCR molecule is cryptic. Therefore, the frequency of T C R peptide-reactive T cells might be very low and strong immunization is necessary for the induction of overt T cell response.
Modulation of phagocytosis in peripheral monocytes and alveolar macrophages from normal subjects and chronic bronchitis patients by synthetic bombesin F. Meloni, P. Ballabio, P. Mangiarotti, L. Bianchi and G. Gialdroni Grassi
Chair of Chemotherapy and Institute of Respiratory Diseases, University of Pavia, Pavia, Italy Bombesin (BN)-related peptides (BRP) are present in humans in many body systems with a variety of biological activities. They exert trophic action in the lung during foetal life and are mitogenic for normal bronchial epithelial cells, and pulmonary fibroblasts. Increased levels of BRP have been described in the lung of cigarette smokers and in smoking related diseases. BRP have also been involved in the network of neuroimmune interactions having shown to be chemotactic for human monocytes (Mo) and to modulate phagocytic function of murine peritoneal macrophages. Wiedermann and coll. showed that human Mo and guinea pig alveolar macrophages (AM) contain appreciable amounts of BRP. We also detected higher BRP levels in Mo and AM of chronic bronchitis (CB) patients compared to normals. Aim of this study is to assess the influence of BN on the in vitro phagocytosis of Mo and AM from a group of CB patients (n = 22) and a group of normal subjects (n = 21). Phagocytosis (calculated as phagocytosis index = Phi and phagocytosis frequency = PhF) was performed on Mo and AM preincubated for 60'_+ BN (concentrations range: 1010 Mol). BN pretreatment significantly enhanced the Phi of Mo and AM in both groups of subjects in a dose-dependent manner. In the CB group, BN activity
was more pronounced: mean Phi value of Mo was 1.88_+ 0.46 in control cells and 3.067_+ 0.55 in cells pretreated with BN 10 Mol. Our preliminary data, showing that BN can interfere in some phagocytic functions, may imply a potential immunomodulating role for BRP in lung response to some pathological noxae.
Proposed role of apoptosis in the immunopathology and immunoregulation of experimental autoimmune encephalomyelitis M.P. Pender, P.A. McCombe, G. Yoong and K.B. Nguyen
Neuroimmunology Research Unit, Department of Medicine, The University of Queensland, Royal Brisbane Hospital, Brisbane, Australia We have recently reported that apoptosis (programmed cell death) occurs in the nervous system in experimental autoimmune encephalomyelitis (EAE) induced by inoculation with myelin basic protein (MBP) in the Lewis rat (J. Neurol. Sci. (1991) 104, 81-87). Here we show, using immunocytochemistry, that about half of the apoptotic cells in the spinal cord of Lewis rats with acute MBP-EAE are a/~ T Iymphocytes. Apoptosis has recently been shown to provide a mechanism of thymic and peripheral tolerance through the clonal elimination of immature and mature T cells. We, therefore, hypothesize that apoptosis of MBPspecific T cells in the nervous system contributes to the subsidence of inflammation and, if ongoing, to the acquisition of tolerance after an attack of acute EAE. Furthermore, some of the apoptotic cells in the spinal cord are likely to be oligodendrocytes. As apoptosis is a mechanism by which cytotoxic T cells kill their targets, we also propose that oligodendrocyte apoptosis occurs in E A E as a result of MBP-specific T cell cytotoxicity and that this is an important mechanism of demyelination in EAE.
CD4 + T cells and cytokines in murine EAE Toufic Renno, Rana Zeine, Marc Girard and Trevor Owens
McGill University, Montreal Neurological Institute, Montreal, Quebec, Canada In experimental allergic encephalomyelitis (EAE), CD4 + T cells infiltrate the CNS to induce disease. We have examined cytokine production by infiltrating CD4 + T cells in S J L / J mice with spinal cord or MBP-induced EAE. PCR amplification of R N A from whole CNS showed a strong increase in levels of m R N A for CD3, IL-2, IFN-y and TNF-a over barely detectable levels in unimmunized mice. Immunoperoxi-