What Is The Role Of T Cells – Differential profiles of cytokines, chemokines and coagulation mediators associated with severity of dengue virus infection in Brazilian patients

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What Is The Role Of T Cells

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Author: Maheshi Mapalagamage Maheshi Mapalagamage Scilit Preprints.org Google Scholar 1, 2, Daniela Weiskopf Daniela Weiskopf Scilit Preprints.org Google Scholar 2, Alessandro Sette Alessandro Sette Scilit Preprints.org Google Scholar 2, 3 and Aruna Dharshan De Silva Aruna Dharshan De Silva Scilit Preprints.org Google Scholar 2, 4, *

Piezo1 Channels Restrain Regulatory T Cells But Are Dispensable For Effector Cd4+ T Cell Responses

Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, United States

Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, United States

Received date: December 18, 2021 / Revision date: January 14, 2022 / Accepted date: January 15, 2022 / Publication date: January 25, 2022

Arbovirus infections such as chikungunya (CHIKV), dengue (DENV) and Zika virus (ZIKV) are a major disease burden in tropical and subtropical countries, and there are currently no effective vaccines or treatments. When designing effective vaccines, it is important to understand the role of T cell responses. Currently, comprehensive identification of T cell epitopes during DENV infection demonstrates that CD8 and CD4 T cells and their specific phenotypes play protective and pathogenic roles. The protective role of CD8 T cells in DENV is achieved by killing infected cells and producing proinflammatory cytokines, as CD4 T cells enhance the activity of B cells and CD8 T cells. Limited studies have attempted to determine the involvement of T cells in CHIKV and ZIKV infection. The identification of human immunodominant ZIKV viral epitopes that respond to specific T cells is sparse, and no epitope has been identified against CHIKV. In CHIKV infection, CD8 T cells are activated in the acute phase in lymph nodes/blood and CD4 T cells are activated in the chronic phase in joints/muscles. Research on the role of T cells in ZIKV neuropathogenesis is limited and requires further exploration. Many studies have shown that the regulatory role of T cells is an important factor to consider when developing effective vaccines due to cross-reactivity between DENV-ZIKV mixed infections and between repeated heterologous/homologous DENV infections.

Quorum Sensing Allows T Cells To Discriminate Between Self And Nonself

Chikungunya virus (CHIKV), dengue virus (DENV), and Zika virus (ZIKV) are widespread arboviruses transmitted by Aedes mosquitoes that cause a significant disease burden in tropical and subtropical regions of the world. CHIKV is an alphavirus (family Togaviridae ) and DENV and ZIKV are flaviviruses (family Flaviviridae ) [1] . These viral infections are endemic in largely overlapping geographic areas. They first appeared in Africa, where CHIKV, DENV, and ZIKV infections are common (Fig. 1).

DENV and ZIKV are enveloped viruses with a single-stranded 10.7 kb positive-sense RNA genome that is translated into a single polyprotein that is cleaved into three structural proteins (C, prM/M, E) and seven non-structural proteins (NS1, NS2A, NS2B), NS3, NS4, NS5A and NS5B), which are acted upon by viral and host proteases [3, 4]. CHIKV encodes three structural proteins (C, E1, E2) and four non-structural proteins (nsP1-4) [5]. Common signs and symptoms of CHIKV, DENV and ZIKV infection include fever, headache, rash, arthralgia and myalgia [6].

Despite extensive global research over the past few decades, there are still limited commercially available antiviral drugs or vaccines for these infections. Treatment usually includes analgesics, anti-inflammatory drugs, and supportive care. Dengvaxia

Sanofi Pasteur’s vaccine is believed to be the first licensed DENV vaccine. However, recent studies have cast doubt on Dengvaxia’s efficacy and raised safety concerns

Role Of Cytokines In Thymus Versus Peripherally Derived Regulatory T Cell Differentiation And Function

Because vaccine recipients with no previous exposure to dengue are at higher risk for hospitalization from severe dengue infection [7,8,9]. In addition to Dengvaxia, there are 16 dengue vaccine candidates in clinical and preclinical trials [ 10 ]. Nearly 20 ZIKV vaccine candidates are being tested through different methods, and three different vaccines are in clinical trials: 1. Inovio (GLS5700), prME against ZIKV [11]; 2. NIAID: VRC-ZKADNA085-00-VP ( VRC 5288); 3. VRC-ZKADNA090-00-VP (VRC 5283) [12]. More than 18 CHIKV vaccine candidates are being studied globally, including advanced formulations such as TSI-GSD-218, which has completed phase II trials, and VRCCHKVLP059-00-VP, which is in phase II trials [13, 14].

The issue of potential cross-reactivity between DENV and ZIKV, as well as the impact of multiple heterologous and homologous DENV infections on T cell responses, has important implications for understanding natural immune patterns and for the development of diagnostic tests and vaccines. Cross-reactivity at the serological and T-cell levels has been reported for DENV, CHIKV, and ZIKV infections. However, its impact on infection and disease is not fully understood. Therefore, the role of T cells in CHIKV, DENV and ZIKV infection; T cells recognize specific viral epitopes; the cross-reactivity between DENV and ZIKV and between heterologous DENV infections is discussed below with the aim of understanding the research during vaccine design. The importance of T cell immunity.

Since T cells play a critical role in immunity and pathogenesis, it is important to identify molecular epitopes recognized in response to infection. In humans, the immunological dominance of these epitopes can be characterized by their ability to bind HLA class I and class II molecules and the binding efficacy of these epitopes to T cell receptors (TCRs). Not all peptides have the ability to exhibit high immune advantage. Therefore, there is a need to study the most immunodominant peptides in viruses, which can be considered as potential targets for epitope-based vaccination. In turn, this will allow the definition of T cell phenotypes relevant to natural immunity and vaccination, which can help resolve how the nature of epitopes and/or the nature of responding T cells is affected by multiple infections. Therefore, this section analyzes the results regarding CHIKV, DENV and ZIKV epitopes identified by our group and others using data provided in the Immune Epitope Database (IEDB: www.IEDB.org, (accessed 30 November 2021) Published data. A previously published review by our team provided a descriptive analysis of human T cell responses to DENV infection based on DENV-specific data available from IEDB as of July 2019 [15].

Immunodominant epitopes for CHIKV, DENV and ZIKV were retrieved from the IEDB database on 30 November 2021 using the following search parameters; any epitope, only positive detections, organism: Dengue virus (ID: 12637)/Chipore Kenya virus (ID: 37124)/Zika virus (ID: 64320), no B cell detection, no MHC ligand detection, host: human (Homo sapiens), disease: infectious.

Role Of T And B ;lymphocytes In Pulmonary Host Defences

Thus, for DENV, the IEDB lists 832 and 1364 DENV T-cell epitopes restricted by HLA class I and class II, respectively, in humans. There are a total of 69 references in the IEDB database, 57 of which are described in detail by Tian et al. (2018)[15]. An immunoinformatics study demonstrated that the HTLWSNGVL and FTTNIWLKL epitope peptides in the NS1 protein sequence could serve as potential agents for polycytotoxic T lymphocyte (CTL) epitope vaccines [16] .

Despite numerous studies and reviews on DENV, very limited references are available for ZIKV infection epitope identification. As of November 2021, only 10 references are available in the IEDB human sample database. Seven studies also looked at CD4

T cell response [26]. Among these studies, only 33 HLA class I-restricted epitopes and 215 HLA class II-restricted epitopes of ZIKV-T cell epitopes identified in humans were recorded in the IEDB. Figure 2 provides a comparison of the number of epitopes recorded in IEDB with the HLA I and HLA II restrictions of protein regions corresponding to immunodominant epitopes in DENV and ZIKV. The highest percentage of ZIKV dominant epitopes reactive to both HLA I (57.6%) and HLA II (36.3%) occurred in the E protein region. In contrast, the highest percentages of DENV dominant epitopes for HLA I and HLA II were found in the NS3 protein region (25.7%) and the NS5 protein region (18.1%), respectively. GLDFSDLYY Restrictive HLA I Yes

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