Priming of T cell responses to viral 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 intravital 2-photon microscopy. A major goal is to understand how T cells are activated in response to viral infections. T cells (both CD4+ and CD8+) are first activated in draining lymph nodes via interactions with dendritic cells (DC) presenting viral antigens. Using well-established models of localised or systemic viral infection, we are directly examining T cell responses by 2-photon microscopy in the skin, lymph nodes (Movie 1) and spleen. We have assembled an array of powerful tools, including recombinant viruses and transgenic mice expressing fluorescent molecules in various compartments.
Movie 1: Dynamic clustering of CD4+ T cells in the lymph node after HSV-1 infection.
Antigen-specific CD4 T cells (green,) CD8+ T cells (white), TRITC+ migratory DC (red).
- Spatiotemporally Distinct Interactions with Dendritic Cell Subsets Facilitates CD4(+) and CD8(+) T Cell Activation to Localized Viral Infection.
Hor JL, Whitney PG, Zaid A, Brooks AG, Heath WR, Mueller SN.
Immunity 2015 Sep 15;43(3):554-65. doi: 10.1016/j.immuni.2015.07.020. Epub 2015 Aug 18.
- Rapid cytotoxic T lymphocyte activation occurs in the draining lymph nodes after cutaneous herpes simplex virus infection as a result of early antigen presentation and not the presence of virus.
Mueller SN, Jones CM, Smith CM, Heath WR, Carbone FR.
J Exp Med 2002 Mar 4;195(5):651-6. PMID: 11877488
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