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Notes: Epithelial expression of class II antigens encoded by the major histocompaatility complex (MHC) has been proposed as a means by which autoimmune thyroid disease may be initiated and maintained. We studied a rat thyroid epithelial cell line (FRTL-5), which constitutively expresses class I (OX18) but not class II (OX6orOX17)determinants to quantify in vitro MHC antigen induction using flow cytometry. Recombinant rat γ interferon (rlFN-γ) induced dosedependent expression of OX6(l-A) antigen at 〉48 h (maximum 80–90% of cells in culture at 100 U/ml). whieh was abrogated by DB-I, a munoclonal antibody to rat IFN-γ OXI7 antigen (I-E) was also induced (86%) and OX18 (class I) markedly increased under these conditions Other thyroid-active agents including the calcium ionophore A23187. dibutyryl cyclic AMP. thyroid-stimulating autoantibodies from Graves’ disease patients (LATS), and TSH. caused no I-A induction. Supernatants from spleen cells stimulaled with plant lectins(concanvialin A or phytohaemagglutinin). but not lectin alone. evoked substantial class II induction. which was inhibited yy DB-1. These findings suggest that IFN-γ is the central mediator of thyroid epithelial class II expression, FRTL'S provides a powerful model for the analysis of thyroid MHC elass 11 dynamies and a potential means of analysing the role of epithelial class II in autoimmune pathogenesis.

Notes: In a pure population of rat bone marrow-derived mononuclear phagocytes (BMMø), the expression of major histocompatibility complex (MHC) molecules and ability to manifest tumoricidal activity were simultaneously studied. Resting BMMø, which express low levels of MHC class II molecules and do not manifest tumoricidal activity, become strongly MHC class II-positive, and evolve tumoricidal activity within 24 h when incubated with macrophage-activating lymphokines (MAF) or gamma interferon (IFN-γ). In contrast, BMMø which were interacted for 24 h with heat-killed microbial agents (Corynebacterium parvum, Listeria) evolve tumoricidal activity without parallel enhancement of MHC class II expression. IFN-α,β neither induced tumoricidal activity nor enhanced MHC class II expression. Further experiments have shown that (a) the kinetics of MAF- and/or IFN-γ-induced amplification of MHC class II expression and of tumoricidal activity are different; (b) enhancement of MHC class II expression by rIFN-γ is not invariably paralleled by induction of tumoricidal activity; and (c) inhibitors of macrophage tumoricidal activity differ in their ability to affect MHC class II expression. It is concluded from these findings that in a population of pure BMMø, i.e. in the complete absence of lymphocytes, the expression of MHC molecules and induction of tumoricidal activity are independently regulated phenomena; in particular, the enhanced expression of MHC class II molecules is not a prerequisite for induction and/or manifestation of tumoricidal activity by mononuclear phagocytes.

Notes: The subset composition of the migrating lymphocyte pool is largely unknown. In order to determine the number of B, T, CD8 +, CD4+ and CD4+‘naive’(CD45RC+) and ‘memory’ (CD45RC−) lymphocytes in this pool, the thoracic duct lymph of the rat was drained for 7 days. The effect of lymphocyte deplction on the number of blood lymphocytes was also monitored. In addition, the influence of continuously applied interferon-γ (IFN-α) on the mobilization of the migrating lymphocyte pool was investigated.Within 1 week 2 × 109 thoracic duct lymphocytes (TDL) were collected, which represents about 50% of the total lymphocyte pool of an adult rat. Among the migrating lymphocytes an early and a late mobilized population could be differentiated. In the former the CD4+‘naive’ (CD45RC+) T lymphocytes constituted the largest population, whereas in the latter it was the B lymphocytes.Continuous infusion of IFN-γ did not affect the number of lymphocytes in the blood. In contrast, in the thoracic duct IFN-γ reduced the appearance of all lymphocyte subsets. However, the pattern of reduction over time differed markedly depending on the population (early or late mobilized) and the phenotype (B- or T-tymphocyte subsets.

Notes: [Auszug] HDV superinfects patients with an acute or chronic hepatitis. It has been implicated in acute fulminant hepatitis B2, and, more importantly, infects chronic carriers of hepatitis B3'4. Up to 20-30% of all exacerbations of chronic carriers of HBV have been reported to be caused by hepatitis delta ...

Notes: Summary The ability of recombinant Interferon-γ to induce class II expression in vitro on pancreatic islet B cells has been investigated by exposing islets isolated from BB/E and normal Wistar rats to Interferon- y and then staining successively with monoclonal antibodies specific for rat class II MHC antigens and insulin. Induction of class 11 expression was never observed on islet cells obtained from either normal Wistar rats or rats from the BB/E low diabetes incidence (〈 2%) subline. In contrast, pancreatic B cells from rats from the BB/E high diabetes incidence (60–70%) subline expressed class II antigen following culture with Interferon-γ.

Notes: Summary A study of Class I and II major histocompatibility complex gene product expression by a rat insulinoma cell line (RINm5F) was performed using monoclonal antibodies and immunoperoxidase techniques. RINm5F cells were incubated with different concentrations of gamma interferon. RINm5F cells exhibit low levels of Class I molecules and are normally devoid of Class II gene products. Upon exposure to gamma interferon, RINm5F cells showed a dramatic increase in Class I expression. This expression was homogenous and could be detected on all cells after 18 h of incubation with as little as 1 unit/ml of interferon. In contrast, de novo Class II expression was not homogeneous and required 36 h of incubation with 10 units/ml of interferon. The number of RINm5F cells expressing Class II antigens was dose- and time-dependent. Interferon treatment did not affect the morphology of RINm5F cells as determined by ultrastructural analysis. Withdrawal of interferon from the culture medium for as long as 78 h diminished but did not abolish the expression of Class I and Class II molecules already induced. The ability of interferon to enhance expression of Class I gene products and induce de novo expression of Class II molecules on B-cell-derived RINm5F cells supports the hypothesis that aberrant expression of major histocompatibility complex gene products on pancreatic B cells may be an important factor in triggering the immune response in Type 1 (insulin dependent) diabetes mellitus.

Notes: Abstract Several factors may inhibit the activity of IFNs. Some of these occur naturally, others are therapy-induced or artificial. Naturally occurring antibodies appear to have a much broader reactivity than therapy-induced antibodies. Naturally induced antibodies are reported in patients suffering from chronic graft-versus-host disease after bone marrow transplantation. Differences in the reported immunogenicity between interferons may not be due to the minor variation in amino acid sequence. The clinical significance of therapy-induced antibodies has been unclear. In patients treated for chronic hepatitis C, antibody formation is closely related to relapse. In animal studies the efficacy of treatments targeting the IFN receptor interaction has been shown. Soluble IFN-γ receptor inhibits the development of autoimmune diseases in mice. Monoclonal antibodies to the IFN-α receptor protects against allograft rejections in monkeys. Two naturally occurring inhibitors of IFN action were reported. The clinical significance and structure of these inhibitors remain elusive.

Notes: Abstract Cytokines participate in many physiological processes including the regulation of immune and inflammatory responses. These effector molecules are produced transiently and locally controlling the amplitude and duration of the response. A variety of experiments has shown that excessive or insufficient production may significantly contribute to the pathophysiology of a range of diseases. Particularly cytokines released by CD4+ T cells at the onset of an immune response are thought to be decisive for pathological or physiological consequences. The meeting in Budapest was focussed on cytokines known to contribute to the pathophysiology of autoimmune diseases, infectious diseases and allograft rejection (e.g., IL-1, IL-4, IL-6, IL-10, IL-12, TNF-α and IFN-α,-β,-γ). A central role for IFN-γ in autoimmunity was suggested by blocking experimentsin vivo using monoclonal antibodies and soluble forms of the IFN-γ receptor (IFN-γsR). These agents ameliorated disease development in a variety of experimental autoimmune diseases in rodents. In a mouse model for the human disease Myasthenia gravis, IFN-α was found to reduce both the incidence and progression of the disease. Treatment of R. aurantiacus-infected mice with anti-IL-4 monoclonal antibodies (mAbs) was reported to interfere with the regression of granulomas in spleen and liver, most likely through inadequate IL-4-mediated suppression of IFN-γ production. In addition, it was shown that mice with disrupted IFN-γ R genes died rapidly after infection with the BCG strain of M. bovis, whereas normal mice survived the infection. IL-12 was found to be the main inductor of IFN-γ during the lethal Shwartzman reaction. TNF-α was identified as the principal cause of mortality after the second injection with LPS. In a variety of studies examining the role of cytokines in the pathogenesis of AIDS, much attention was given to thein vitro effects of HIV-1 and/or the HIV-1 viral membrane protein gp120 on triggering cytokine production by peripheral blood leukocytes (PBLs) and purified monocytes/macrophages (Mø) originating from healthy donors. Gp120 as a sole agent significantly suppressed IFN-γ production by mitogen-stimulated PBLs and induced the production of IFN-α in cultures of normal human peripheral blood mononuclear cells (PBMCs). In a human macrophage cell line, TNF-α exerted a stimulatory effect on viral replication and programmed cell death induced by HIV-1 which was potentiated by the simultaneous incubation with IFN-γ. Upon transfection of human PBLs and CD4+ T cells with a retroviral vector encoding human IFN-β, a notable reduction in reverse transcriptase activity after HIV-1 challenge was observed. Gp120 was also found to induce both IL-6 and TNF-α expression and to induce morphological changes reminiscent for apoptosis in primary astrocytes and in a re-aggregated human brain cell model, suggesting a role for these cytokines in the neuropathology of AIDS dementia. Moreover, data were presented indicating that cytokine-induced expression of cell adhesion molecules (e.g., ICAM-1) in HIV-1 infected U 937 cells leads to high level incorporation of this molecule in the membrane of the viral progeny which may play a role in the attachment of such virions to CD4-negative cells.