Immune responses against persistent viral infections: possible avenues for immunotherapeutic interventions.
ABSTRACT Persistent viral infections present a significant threat to society, and treatment options for infected individuals are in urgent demand. During viral persistence, the balance between the virus and the host immune response is crucial. The immune system keeps the virus in check, and the virus counters by evading the immune response to avoid clearance, ultimately tipping the balance in favor of the virus and causing disease in many cases. Thus, efforts to tip the balance in favor of the host through immunotherapy holds promise for establishing control of viral replication. However, in most persistent viral infections, the continuous presence of the viral antigen renders virus-specific T cells to become dysfunctional. These differences can range from severe functional impairments in high-load persistent infections, to more subtle changes in infections with a lower virus burden. Recent work has shed light on immunoregulatory molecules or cytokines that affect viral persistence and/or T-cell function, and interventions that modulate these factors have led to effective viral control in experimental models. Exploitation of these experimental therapies may lead to treatments that would be of great clinical benefit to patients suffering from persistent virus infections, such as HIV, HBV, or HCV, or the herpesviruses CMV and EBV.
SourceAvailable from: Osman Sinanović
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ABSTRACT: Uveitis is a potentially blinding inflammatory disease. 30-50% of uveitis cases are considered idiopathic. The present study sought to determine intraocular cytokine patterns in different etiological types of uveitis in order to better understand their immunological regulation and determine whether the cytokine pattern may be a useful diagnostic tool. From a multicenter institutional prospective study, clinical and biological datas from patients with various etiologies of uveitis, determined after a complete work-up, were compared with a control group of cataract patients. Multiplex assay was used to assess the profiles of 27 cytokines and chemokines in aqueous humor samples from these patients. In total, 62 patients with infectious or non-infectious uveitis and 88 controls were included. After a complete work-up, the cause of uveitis remained unknown in 25 patients (40% idiopathic uveitis). IL-1β levels were markedly increased in viral uveitis, as were IL-10 levels, whereas IL-17A levels were augmented in toxoplasmic uveitis. Based on the cytokine pattern, patients were reassigned to specific groups. At the end, the diagnosis of idiopathic uveitis was still valid in only 11 patients (18%). The observation that some markers are specific to certain diseases enables a better understanding of the disease pathogenesis and paves the way for new diagnostic methods aimed at identifying inflammatory markers, which may perhaps be targeted by therapy.Clinical and vaccine Immunology: CVI 11/2014; 22(1). DOI:10.1128/CVI.00423-14 · 2.37 Impact Factor
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ABSTRACT: Intracellular pathogens are capable of inducing vigorous CD8+ T cell responses. However, we do not entirely understand the factors driving the generation of large pools of highly protective memory CD8+ T cells. Here, we studied the generation of endogenous ovalbumin-specific memory CD8+ T cells following infection with recombinant vesicular stomatitis virus (VSV) and Listeria monocytogenes (LM). VSV infection resulted in the generation of a large ovalbumin-specific memory CD8+ T cell population, which provided minimal protective immunity that waned with time. In contrast, the CD8+ T cell population of LM-ova provided protective immunity and remained stable with time. Agonistic CD40 stimulation during CD8+ T cell priming in response to VSV infection enabled the resultant memory CD8+ T cell population to provide strong protective immunity against secondary infection. Enhanced protective immunity by agonistic anti-CD40 was dependent on CD70. Agonistic anti-CD40 not only enhanced the size of the resultant memory CD8+ T cell population, but enhanced their polyfunctionality and sensitivity to antigen. Our data suggest that immunomodulation of CD40 signaling may be a key adjuvant to enhance CD8+ T cell response during development of VSV vaccine strategies.PLoS ONE 08/2014; 9(8):e106060. DOI:10.1371/journal.pone.0106060 · 3.53 Impact Factor