scholarly journals CMV-Specific Cell-Mediated Immunity in Immunocompetent Adults with Primary CMV Infection: A Case Series and Review of the Literature

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 816
Author(s):  
Angela Chiereghin ◽  
Gabriella Verucchi ◽  
Tiziana Lazzarotto

Cytomegalovirus-specific cell-mediated immunity (CMV-CMI) in actively infected healthy immunocompetent hosts has been poorly investigated. Conversely, correlates of maternal protective immunity for the fetus after primary infection in pregnancy continue to be studied. The kinetics and magnitude of CMV-specific CMI in immunocompetent primary CMV-infected adults are described. A literature review on CMV-CMI in primarily infected pregnant women and its correlation to the risk of vertical virus transmission is included. Immunological measurements after infection were performed by enzyme-linked ImmunoSPOT assay enumerating IFN-γ secreting CMV-specific T cells, at a single cell level, upon in vitro stimulation with viral antigens. Simultaneously, serological and virological profiles of infected patients were investigated. Patients displayed mild-to-moderate clinical and laboratory profiles for infection, and all showed positive EliSpot results in the early stage of infection (<20 days after onset). The virus-CMI was strong in the majority of patients (58.8%) in which the lowest CMV-DNAemia levels (<300 copies/mL) were detected. Significantly higher viral loads were observed in patients with weak CMV-CMI at the same time-point post-infection (up to 15,104 copies/mL; p < 0.001). T cell response magnitudes to IE-1 and pp65-UL83 peptides were overlapping and stable over time. In these case series, the early presence of CMV-CMI was probably pivotal in controlling viral replication and led to spontaneous viral clearance.

2021 ◽  
Vol 8 ◽  
Author(s):  
Paola M. Boggiatto ◽  
Carly R. Kanipe ◽  
Mitchell V. Palmer

Bovine tuberculosis (bTB), caused by infection with Mycobacterium bovis, continues to be a major economic burden associated with production losses and a public health concern due to its zoonotic nature. As with other intracellular pathogens, cell-mediated immunity plays an important role in the control of infection. Characterization of such responses is important for understanding the immune status of the host, and to identify mechanisms of protective immunity or immunopathology. This type of information can be important in the development of vaccination strategies, diagnostic assays, and in predicting protection or disease progression. However, the frequency of circulating M. bovis-specific T cells are often low, making the analysis of such responses difficult. As previously demonstrated in a different cattle infection model, antigenic expansion allows us to increase the frequency of antigen-specific T cells. Moreover, the concurrent assessment of cytokine production and proliferation provides a deeper understanding of the functional nature of these cells. The work presented here, analyzes the T cell response following experimental M. bovis infection in cattle via in vitro antigenic expansion and re-stimulation to characterize antigen-specific CD4, CD8, and γδ T cells and their functional phenotype, shedding light on the variable functional ability of these cells. Data gathered from these studies can help us better understand the cellular response to M. bovis infection and develop improved vaccines and diagnostic tools.


2018 ◽  
Vol 3 (29) ◽  
pp. eaao2892 ◽  
Author(s):  
Lies Boelen ◽  
Bisrat Debebe ◽  
Marcos Silveira ◽  
Arafa Salam ◽  
Julia Makinde ◽  
...  

Killer cell immunoglobulin-like receptors (KIRs) are expressed predominantly on natural killer cells, where they play a key role in the regulation of innate immune responses. Recent studies show that inhibitory KIRs can also affect adaptive T cell–mediated immunity. In mice and in human T cells in vitro, inhibitory KIR ligation enhanced CD8+ T cell survival. To investigate the clinical relevance of these observations, we conducted an extensive immunogenetic analysis of multiple independent cohorts of HIV-1–, hepatitis C virus (HCV)–, and human T cell leukemia virus type 1 (HTLV-1)–infected individuals in conjunction with in vitro assays of T cell survival, analysis of ex vivo KIR expression, and mathematical modeling of host-virus dynamics. Our data suggest that functional engagement of inhibitory KIRs enhances the CD8+ T cell response against HIV-1, HCV, and HTLV-1 and is a significant determinant of clinical outcome in all three viral infections.


2020 ◽  
Vol 6 (2) ◽  
Author(s):  
Ciro Manzo

The role of hydroxychroloquine (HCQ) sulfate as therapeutic option in coronavirus disease 2019 (COVID-19) patients aroused great interest and hope, so much so as to authorize several studies in the world. Despite the beneficial effects demonstrated in vitro and in some case-series, doubts remain about its clinical use, so that at present more than 20 different therapeutic study protocols have been proposed. Very recently, a protocol has been authorized by the Italian Medicines Agency (AIFA), in order to evaluate the efficacy of out-of-hospital treatment with HCQ in the reducing viral loads and need for hospitalization in symptomatic COVID-19 infected patients who are confined at home. The article describes lights and shadows of HCQ therapy in the elderly and geriatric patients affected by COVID-19, and suggests that the geriatrician should use HCQ only after careful patient selection and be aware of its pharmacokinetic properties and adverse effects, before better-designed studies determine their benefit, if any, in treating COVID-19.


2018 ◽  
Vol 7 (2) ◽  
pp. 55-60
Author(s):  
Marina Spinu ◽  
Pall Emoke ◽  
Niculae Mihaela ◽  
Brudascã Florinel ◽  
Vasiu Aurel ◽  
...  

2012 ◽  
Vol 93 (6) ◽  
pp. 1204-1214 ◽  
Author(s):  
Lázaro Gil ◽  
Lídice Bernardo ◽  
Alequis Pavón ◽  
Alienys Izquierdo ◽  
Iris Valdés ◽  
...  

The interplay of different inflammatory cytokines induced during dengue virus infection plays a role in either protection or increased disease severity. In this sense, vaccine strategies incorporating whole virus are able to elicit both functional and pathological responses. Therefore, an ideal tetravalent vaccine candidate against dengue should be focused on serotype-specific sequences. In the present work, a new formulation of nucleocapsid-like particles (NLPs) obtained from the recombinant dengue-2 capsid protein was evaluated in mice to determine the level of protection against homologous and heterologous viral challenge and to measure the cytotoxicity and cytokine-secretion profiles induced upon heterologous viral stimulation. As a result, a significant protection rate was achieved after challenge with lethal dengue-2 virus, which was dependent on CD4+ and CD8+ cells. In turn, no protection was observed after heterologous challenge. In accordance, in vitro-stimulated spleen cells from mice immunized with NLPs from the four dengue serotypes showed a serotype-specific response of gamma interferon- and tumour necrosis factor alpha-secreting cells. A similar pattern was detected when spleen cells from dengue-immunized animals were stimulated with the capsid protein. Taking these data together, we can assert that NLPs constitute an attractive vaccine candidate against dengue. They induce a functional immune response mediated by CD4+ and CD8+ cells in mice, which is protective against viral challenge. In turn, they are potentially safe due to two important facts: induction of serotype specific cell-mediated immunity and lack of induction of antiviral antibodies. Further studies in non-human primates or humanized mice should be carried out to elucidate the usefulness of the NLPs as a potential vaccine candidate against dengue disease.


2021 ◽  
Vol 12 ◽  
Author(s):  
Amber D. Jones ◽  
Svetlana Khakhina ◽  
Tara Jaison ◽  
Erin Santos ◽  
Stephen Smith ◽  
...  

A unique population of HIV-1 infected individuals can control infection without antiretroviral therapy. These individuals fall into a myriad of categories based on the degree of control (low or undetectable viral load), the durability of control over time and the underlying mechanism (i.e., possession of protective HLA alleles or the absence of critical cell surface receptors). In this study, we examine a cohort of HIV-1 infected individuals with a documented history of sustained low viral loads in the absence of therapy. Through in vitro analyses of cells from these individuals, we have determined that infected individuals with naturally low viral loads are capable of controlling spreading infection in vitro in a CD8+ T-cell dependent manner. This control is lost when viral load is suppressed by antiretroviral therapy and correlates with a clinical CD4:CD8 ratio of &lt;1. Our results support the conclusion that HIV-1 controllers with low, but detectable viral loads may be controlling the virus due to an effective CD8+ T-cell response. Understanding the mechanisms of control in these subjects may provide valuable understanding that could be applied to induce a functional cure in standard progressors.


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