SUMMARYThis study was designed to investigate the therapeutic effects of interferon (IFN)-g -modulated dendritic cells (DC) in experimental autoimmune myasthenia gravis (EAMG). We induced EAMG in Lewis rats by immunization with Torpedo nicotinic acetylcholine receptor (nAChR) and adjuvant. On day 33 postimmunization (p.i.), splenic DC were prepared, exposed to IFN-g alone (IFN-g -DC) or to IFN-g in combination with 1-methyl-DL-tryptophan (1-MT), the specific inhibitor of indoleamine 2,3-dioxygenase (IDO) (IFN-g + 1-MT-DC), and injected subcutaneously into rats with incipient EAMG on day 5 p.i. A control group of EAMG rats received naive DC on day 5 p.i., while another group received 1-MT every other day, intraperitoneally (p.i.), from days 5 to 41 p.i. The severity of clinical signs of EAMG was reduced dramatically in IFN-g -DC-treated rats compared to rats receiving naive DC, IFN-g + 1-MT-DC or 1-MT alone. The number of plasma cells secreting nAChR antibodies was reduced and the expression of B cell activation factor (BAFF) on splenic and lymph node mononuclear cells (MNC) was downregulated in rats treated with IFN-g -DC. In vitro co-culture of MNC derived from EAMG rats with IFNg -DC produced relatively few cells secreting nAChR antibodies. Addition of 1-MT to the co-culture significantly increased the number of cells secreting nAChR antibodies. We conclude that IFN-g -DC reduced the number of plasma cells secreting nAChR antibodies in an IDO-dependent manner and ameliorated the development of EAMG in Lewis rats.
BackgroundCharacteristic skin lesions play a key role in clinical diagnosis of spotted fever group rickettsioses and this study describes these cutaneous manifestations along with basic histological features.Methods and FindingsStudy was conducted at Medical Unit, Teaching Hospital, Peradeniya, from November 2009 to October 2011, where a prospective data base of all rickettsial infections is maintained. Confirmation of diagnosis was made when IgM and IgG immunofluorescent antibody titre of 1/32 and >1/256 respectively. Of the 210 clinical cases, 134 had cutoff antibody titers for Rickettsia conorii antigen for confirmation. All these 134 patients had fever and skin rash, and of them 132(98%) had discrete maculopapular rash while eight (6%) had fern leaf type skin necrosis. Eight patients (6%) had healed tick bite marks. Average size of a skin lesion was 5 mm and rash involved 52% of body surface, distributed mainly in limbs and back of the chest. Generally the facial and leg skin was slightly oedematous particularly in old aged patients. Sixteen patients (12%) had pain and swelling of ankle joints where swelling extended to feet and leg. Biopsies from skin rash of six patients showed evidence of cutaneous vasculitis and of them, 247 bp region of the 17-kDa spotted fever group specific protein antigen was amplified using PCR.ConclusionsA discrete maculopapular rash and occasional variations such as fern leaf shape necrosis and arthritis are found in spotted fever group. Histology found vasculitis as the pathology of these lesions.
Human herpesvirus 6A (HHV-6A) is a common virus with a worldwide distribution that has been associated with multiple sclerosis. Whether HHV-6A can replicate in dendritic cells (DC) and how the infection might modulate the functional properties of the cell are currently not well known and need further investigations. Here, we show that a non-productive infection of HHV-6A in DC leads to the up-regulation of HLA-ABC, via autocrine IFN-α signaling, as well as the up-regulation of HLA-DR and CD86. However, HHV-6A exposure reduces IL-8 secretion by DC and their capacity to stimulate allogenic T cell proliferation. The ability to suppress DC functions important for activation of innate and adaptive immune responses might be one successful strategy by which HHV-6A avoids the induction of appropriate host defense mechanisms, and thus facilitating persistent infection.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.