Abstract

Antigen-specific T lymphocytes play a critical role in controlling viral infections. However, we report here that preexisting virus-specific T cell responses also contribute to promoting adenovirus (Ad) infection. Previously, we found that CD14+ monocytes from Ad-seropositive individuals exhibited an increased susceptibility to Ad infection, when compared with that of Ad-seronegative individuals. But the underlying mechanisms for this enhancement of viral infection are not completely clarified. In this study, we found that the efficacy of Ad infection into CD14+ monocytes was significantly decreased after CD3+ T lymphocytes depletion from PBMC samples of Ad-seropositive individuals. In contrast, adding virus-specific CD3+ T lymphocytes into PBMC samples of Ad-seronegative individuals resulted in a significant increase of infection efficacy. CD3+ T lymphocytes in PBMC samples from Ad-seropositive individuals were more sensitive to be activated by adenovirus stimulus, characterized by upregulation of multiple cytokines and activation markers and also enhancement of cell proliferation. Further studies demonstrated that GM-CSF and IL-4 can promote Ad infection by up-regulating the expression of scavenger receptor 1 (SR-A) and integrins αVβ5 receptor of CD14+ cells. And taken together, these results suggest a novel role of virus-specific T cells in mediating enhancement of viral infection, and provide insights to understand the pathogenesis and complicated interactions between viruses and host immune cells.

Highlights

  • When organism is attacked by external microorganisms, immune responses are elicited to fight against these infections, which lead to subtle interactions between host immune cells and microorganisms

  • We further report that preexisting virus-specific CD3+ T lymphocytes contribute to promoting Ad infection into monocytes/macrophages by secreting granulocyte macrophage-colony stimulating factor (GM-CSF) and Interleukin 4 (IL-4) cytokines, which upregulated the expression of scavenger receptor class A (SR-A) and integrins αVβ5 receptor

  • We found that the efficacy of adenovirus infection into CD14+ monocytes was significantly decreased after removing CD3+ T lymphocytes from peripheral blood mononuclear cells (PBMCs) samples of Ad-seropositive individuals

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Summary

Introduction

When organism is attacked by external microorganisms, immune responses are elicited to fight against these infections, which lead to subtle interactions between host immune cells and microorganisms. Compared with innate immune responses, adaptive immune responses are highly specialized, rapid and powerful in response to a particular pathogen. Adaptive immune responses are mainly involved with B lymphocytes-mediated humoral immunity and T lymphocytes-mediated cellular immunity. It is well known that both B cells (by secreting antibodies) and T cells (by producing cytokines and chemokines) play critical roles to prevent and eliminate pathogens [1,2,3]. With the long-term struggle between viruses and their hosts, many viruses have evolved kinds of mechanisms to “turn enemies into allies”, thereby hijacking and converting the immune system for facilitating their entry, replication and spread [4,5,6,7].

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