Cellular immunity and memory to respiratory virus infections

Respiratory virus infections, such as those caused by influenza and parainfluenza viruses, are a major cause of morbidity and mortality worldwide. Current vaccines against these pathogens rely on the induction of humoral immune responses that target viral coat proteins. Although this type of immunity provides solid protection against homologous virus strains, it is ineffective against heterologous virus strains that express serologically distinct coat proteins. In contrast, cellular immune responses can target internal antigens that are shared between heterologous viral strains. This form of immunity, sometimes referred to as heterosubtypic immunity, can mediate a substantial degree of protection. Thus, vaccines that emphasize cellular immune responses would be a valuable complement to available humoral vaccines. However, we only have a rudimentary understanding of which T cell subsets mediate protective immunity, how T cell memory is established and maintained, how that memory is recalled in a secondary infection, and why cellular immunity wanes rapidly with time. Here we review the role of CD4(+) and CD8(+) T cells in the recall response to influenza and parainfluenza viruses. In particular we focus on the recent observation that substantial numbers of memory T cells are established in the lung tissues and discuss the potential role of these cells in mediating a recall response. A thorough understanding of the cellular immune response to infection in the lungs is essential for future vaccine development.