“These cells represent a front line of defence against infectious diseases.”
By Laura Mackay, researcher at Peter Doherty Institute
The research was conducted at the Peter Doherty Institute for Infection and Immunity, a joint venture of the University of Melbourne and the Royal Melbourne Hospital in Australia. The findings have been peer reviewed and published in Immunity (15 December).
Led by Laura Mackay and Francis Carbone, the study identified specialised immune cells that are found to be key to protecting against infection. These memory T cells live in a wide range of tissues and organs, including skin, lung, brain, kidney, liver, salivary glands and reproductive organs rather than in the blood.
“These cells represent a front line of defence against infectious diseases. They are uniquely positioned in tissues of the body where pathogens can enter, and here, they are ready to fight off infection. For example, the malaria parasite grows in the liver. By designing new vaccines that establish tissue-resident memory T cell populations within the liver, these cells will be able to deliver faster, more focused responses at the site where the pathogen is,” Mackay says.
The researchers studied the behaviour of these cells in murine models (also called pre-clinical models) using a variety of laboratory techniques, including intravital 2-photon imaging or the live imaging of cells in real time in the body.
In their experiments, the researchers established tissue-resident memory T cells in the skin and then challenged the skin with virus. They saw elimination of the virus in skin sites where the tissue-resident memory T cells were in place. They were also able to determine the molecular signals required for the development and survival of these cells in the tissue.
“By learning to control these cells, we can harness their protective function to prevent infectious diseases. This would have a fresh focus on how vaccines are created for infectious diseases,” Mackay says.
“For example, to block transmission of viruses such as HIV or herpes, we want to generate immune responses in the skin and reproductive organs. Similarly vaccines against influenza could be made more effective if they are designed to also deposit tissue-resident memory T cells in the lung, where the virus grows. Likewise, vaccines could be designed to establish tissue-resident memory T cells in the liver to protect against malaria,” adds Mackay.
The next phase of research is under way to test ways to convert T cells in the blood to tissue-resident memory T cells, and evaluate their therapeutic potential against a wide range of pathogens.
This piece was produced by SciDev.Net’s South-East Asia & Pacific desk.
Laura K. Mackay and others T-box Transcription Factors Combine with the Cytokines TGF-β and IL-15 to Control Tissue-Resident Memory T Cell Fate (Immunity, 15 December 2015)