Many studies utilise non-physiological ex vivo restimulation of effector and memory T cells as an indication of their ability to perform functions such as cytokine production and cytotoxicity during infection. Nevertheless, the dynamics of effector and memory T cell function, in vivo, during infection, remain lesser defined. Furthermore, it is of interest to delineate the relative contribution of infected and uninfected tissue cells and immune cells in stimulating and/or regulating these pathogen-specific T cell functions.
Using a cutaneous model of HSV infection we demonstrate that non-overlapping APCs in different regions of the infected skin and priming lymph nodes are responsible for stimulating IFN-γ production by effector CD4+ and CD8+ T cells. Additionally, effector (and memory) CD8+ T cells are shown to differ from their naive counterparts in terms of their functional response to HSV-infected and -uninfected cross-presenting APCs. Therefore, we highlight a sophisticated system of segregation of the helper and killer T cell response during localised virus infection, and, provide an example where armed killer T cells are restrained in functionality, potentially limiting the development of host pathology and autoimmunity.