Cellular immunity and memory to respiratory virus infections

Respiratory virus infections, such as those caused by influenza and parainf luenza viruses, are a major cause of morbidity and mortality worldwide. Cur rent vaccines against these pathogens rely on the induction of humoral immu ne responses that target viral coat proteins. Although this type of immunit y provides solid protection against homologous virus strains, it is ineffec tive 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 i mmunity, sometimes referred to as heterosubtypic immunity, can mediate a su bstantial degree of protection. Thus, vaccines that emphasize cellular immu ne responses would be a valuable complement to available humoral vaccines. However, we only have a rudimentary understanding of which T cell subsets m ediate protective immunity, how T cell memory is established and maintained , how that memory is recalled in a secondary infection, and why cellular im munity 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 potentia l role of these cells in mediating a recall response. A thorough understand ing of the cellular immune response to infection in the lungs is essential for future vaccine development.