The CD8 T Cell Response to Respiratory Virus Infections

Abstract

Humans are highly susceptible to infection with respiratory viruses including respiratory syncytial virus (RSV), influenza virus, human metapneumovirus, rhinovirus, coronavirus, and parainfluenza virus. While some viruses simply cause symptoms of the common cold, many respiratory viruses induce severe bronchiolitis, pneumonia, and even death following infection. Despite the immense clinical burden, the majority of the most common pulmonary viruses lack long-lasting efficacious vaccines. Nearly all current vaccination strategies are designed to elicit broadly neutralizing antibodies, which prevent severe disease following a subsequent infection. However, the mucosal antibody response to many respiratory viruses is not long-lasting and declines with age. CD8 T cells are critical for mediating clearance following many acute viral infections in the lung. In addition, memory CD8 T cells are capable of providing protection against secondary infections. Therefore, the combined induction of virus-specific CD8 T cells and antibodies may provide optimal protective immunity. Herein, we review the current literature on CD8 T cell responses induced by respiratory virus infections. Additionally, we explore how this knowledge could be utilized in the development of future vaccines against respiratory viruses, with a special emphasis on RSV vaccination.

Keywords: CD8 T cell; coronavirus; human metapneumovirus; influenza A virus; memory T cell; respiratory syncytial virus; respiratory virus; rhinovirus.

Figure 1

Critical factors for an optimal CD8 T cell-mediated respiratory syncytial virus (RSV) vaccine. A future RSV vaccine designed to elicit a CD8 T cell response will require a balance between CD8 T cell-mediated protection and immunopathology, which may be achieved through the consideration of three important aspects: (1) magnitude, (2) localization, and (3) regulation. An optimal magnitude of the CD8 T cell response will be one that achieves efficient viral clearance in the absence of immunopathology. The vaccination route will be critical in determining the localization of the CD8 T cell response. A pulmonary route of vaccination will induce T_RM in the lung that provides superior protection compared to a systemic immunization that would likely not generate protective T_RM. Lastly, regulation of the CD8 T cell response generated through vaccination will be crucial, as uncontrolled effector functions, particularly IFN-γ production, can result in immunopathology.