Preexisting Virus-Specific T Lymphocytes-Mediated Enhancement of Adenovirus Infections to Human Blood CD14+ Cells

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.