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.