RSV Vaccine-Enhanced Disease Is Orchestrated by the Combined Actions of Distinct CD4 T Cell Subsets

PLoS Pathogens

Stacey M. Hartwig¹  David K. Meyerholz²  Cory J. Knudson³  Steven M. Varga³ 

[1] Department of Microbiology, University of Iowa, Iowa City, Iowa, United States of America;Department of Pathology, University of Iowa, Iowa City, Iowa, United States of America;Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, United States of America

关键词: T helper cells;    Eosinophils;    Immune response;    Cytokines;    Mucus;    Vaccines;    Antibodies;    Mouse models;   

DOI  :  10.1371/journal.ppat.1004757

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

There is no currently licensed vaccine for respiratory syncytial virus (RSV) despite being the leading cause of lower respiratory tract infections in children. Children previously immunized with a formalin-inactivated RSV (FI-RSV) vaccine exhibited enhanced respiratory disease following natural RSV infection. Subsequent studies in animal models have implicated roles for CD4 T cells, eosinophils and non-neutralizing antibodies in mediating enhanced respiratory disease. However, the underlying immunological mechanisms responsible for the enhanced respiratory disease and other disease manifestations associated with FI-RSV vaccine-enhanced disease remain unclear. We demonstrate for the first time that while CD4 T cells mediate all aspects of vaccine-enhanced disease, distinct CD4 T cell subsets orchestrate discrete and specific disease parameters. A Th2-biased immune response, but not eosinophils specifically, was required for airway hyperreactivity and mucus hypersecretion. In contrast, the Th1-associated cytokine TNF-α was necessary to mediate airway obstruction and weight loss. Our data demonstrate that individual disease manifestations associated with FI-RSV vaccine-enhanced disease are mediated by distinct subsets of CD4 T cells.

【 授权许可】

CC BY