Dataset Information

A Paradigmatic Interplay between Human Cytomegalovirus and Host Immune System: Possible Involvement of Viral Antigen-Driven CD8+ T Cell Responses in Systemic Sclerosis.

ABSTRACT: Human cytomegalovirus (HCMV) is a highly prevalent opportunistic agent in the world population, which persists as a latent virus after a primary infection. Besides the well-established role of this agent causing severe diseases in immunocompromised individuals, more recently, HCMV has been evoked as a possible factor contributing to the pathogenesis of autoimmune diseases such as systemic sclerosis (SSc). The interplay between HCMV and immune surveillance is supposed to become unbalanced in SSc patients with expanded anti-HCMV immune responses, which are likely involved in the exacerbation of inflammatory processes. In this study, blood samples from a cohort of SSc patients vs. healthy subjects were tested for anti-HCMV immune responses (IgM, IgG antibodies, and T cells to peptide pools spanning the most immunogenic HCMV proteins). Statistically significant increase of HCMV-specific CD8+ T cell responses in SSc patients vs. healthy subjects was observed. Moreover, significantly greater HCMV-specific CD8+ T cell responses were found in SSc patients with a longer disease duration and those with higher modified Rodnan skin scores. Given the known importance of T cells in the development of SSc and that this virus may contribute to chronic inflammatory diseases, these data support a relevant role of HCMV-specific CD8+ T cell responses in SSc pathogenesis.

SUBMITTER: Arcangeletti MC

PROVIDER: S-EPMC6163388 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Publications

A Paradigmatic Interplay between Human Cytomegalovirus and Host Immune System: Possible Involvement of Viral Antigen-Driven CD8+ T Cell Responses in Systemic Sclerosis.

Arcangeletti Maria-Cristina MC Maccari Clara C Vescovini Rosanna R Volpi Riccardo R Giuggioli Dilia D Sighinolfi Gianluca G De Conto Flora F Chezzi Carlo C Calderaro Adriana A Ferri Clodoveo C

Viruses 20180918 9

Human cytomegalovirus (HCMV) is a highly prevalent opportunistic agent in the world population, which persists as a latent virus after a primary infection. Besides the well-established role of this agent causing severe diseases in immunocompromised individuals, more recently, HCMV has been evoked as a possible factor contributing to the pathogenesis of autoimmune diseases such as systemic sclerosis (SSc). The interplay between HCMV and immune surveillance is supposed to become unbalanced in SSc ...[more]

PMID: 30231575

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Project description:The T-cell receptor (TCR) is a highly polymorphic surface receptor that allows T-cells to recognize antigenic peptides presented on the major histocompatibility complex (MHC). Changes in the TCR repertoire have been observed in several autoimmune conditions, and these changes are suggested to predispose autoimmunity . Multiple lines of evidence have implied an important role for T-cells in the pathogenesis of Systemic Sclerosis (SSc), a complex autoimmune disease. One of the major questions regarding the roles of T-cells is whether expansion and activation of T-cells observed in the diseases pathogenesis is (auto)antigen driven. To investigate the temporal TCR repertoire dynamics in SSc, we performed high-throughput sequencing of CD4+ and CD8+ TCRβ chains on longitudinal samples obtained from four SSc patients collected over a minimum of two years. Repertoire overlap analysis revealed that samples taken from the same individual over time shared a high number of TCRβ sequences, indicating a clear temporal persistence of the TCRβ repertoire in CD4+ as well as CD8+ T-cells. Moreover, the TCRβs that were found with a high frequency at one time point were also found with a high frequency at the other time points (even after almost four years), showing that frequencies of dominant TCRβs are largely consistent over time. We also show that TCRβ generation probability and observed TCR frequency are not related in SSc samples, showing that clonal expansion and persistence of TCRβs is caused by antigenic selection rather than convergent recombination. Moreover, we demonstrate that TCRβ diversity is lower in CD4+ and CD8+ T-cells from SSc patients compared to healthy memory T-cells, as SSc TCRβ repertoires are largely dominated by clonally expanded persistent TCRβ sequences. Lastly, using “Grouping of Lymphocyte Interactions by Paratope Hotspots” (GLIPH2), we identify clusters of TCRβ sequences with homologous sequences that potentially recognize the same antigens and contain TCRβs that are persist in SSc patients. In conclusion, our results show that that CD4+ and CD8+ T-cells are highly persistent in SSc patients over time, and this persistence is likely a result from antigenic selection. Moreover, persistent TCRs form high similarity clusters with other (non-)persistent sequences, that potentially recognize the same epitopes. These data provide evidence for an (auto-)antigen driven expansion of CD4/CD8+ T-cells in Ssc.

Dataset Information

A Paradigmatic Interplay between Human Cytomegalovirus and Host Immune System: Possible Involvement of Viral Antigen-Driven CD8+ T Cell Responses in Systemic Sclerosis.

Publications

A Paradigmatic Interplay between Human Cytomegalovirus and Host Immune System: Possible Involvement of Viral Antigen-Driven CD8+ T Cell Responses in Systemic Sclerosis.

Similar Datasets

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