Memory CD4 T cell-mediated immunity against influenza A virus: more than a little helpful

Abstract

Recent observations have uncovered multiple pathways whereby CD4 T cells can contribute to protective immune responses against microbial threats. Incorporating the generation of memory CD4 T cells into vaccine strategies thus presents an attractive approach toward improving immunity against several important human pathogens, especially those against which antibody responses alone are inadequate to confer long-term immunity. Here, we review how memory CD4 T cells provide protection against influenza viruses. We discuss the complexities of protective memory CD4 T cell responses observed in animal models and the potential challenges of translating these observations into the clinic. Specifically, we concentrate on how better understanding of organ-specific heterogeneity of responding cells and defining multiple correlates of protection might improve vaccine-generated memory CD4 T cells to better protect against seasonal, and more importantly, pandemic influenza.

Figure 1

Homotypic versus Heterosubtypic immunity against IAV. Homotypic immunity is mediated by neutralizing and protective antibodies generated upon infection or vaccination with a virus expressing the same external coat proteins (NA and HA). Heterosubtypic immunity is mediated largely by memory T cells that recognize internal viral proteins shared between the priming and challenge virus.