Imaging the priming of CD8 Killer T cell responses to Herpes Simplex Virus-1 skin infection
Much of our understanding of the complex series of events that occur during the priming of immune responses to infections or following vaccination have been gained via static methods such as flow cytometry, histology and cell culture. These methods provide limited information on when, where and how different cells interact during the different phases of immunity. We now have the ability to follow immune cells within living tissues and animals to determine their behaviour in real time using 2-photon laser scanning microscopy (Mueller, Current Opinion in Immunology 2010; 22: 293–298). Many natural infections, such as Herpes Simplex Virus (HSV) and Influenza virus, target peripheral sites in the body and remain localised, requiring the cells of the immune system to migrate to tissues such as the skin and lungs to defeat the pathogen. To achieve this, T cells (both CD4+ and CD8+) are first activated in draining lymph nodes via interactions with dendritic cells (DC) presenting viral antigens. At present, we know little about where and how antiviral T cell responses are primed within the lymph nodes following infection with pathogens that remain localised in the periphery. To examine this, we are using a well-established model of cutaneous HSV infection, along with T cell receptor transgenic mice specific for HSV, to directly examine T cell responses by 2-photon microscopy (Movies 1 & 2). We have assembled an array of powerful tools, including HSV-1 recombinants and transgenic mice expressing fluorescent molecules in various compartments. We are currently using these novel tools to visualise the dynamic interactions that occur between T cells and dendritic cells in the lymph nodes of live mice after HSV infection of the skin.
NB: this is a collaborative project with the Mueller group.
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