Regulatory T Cells Limit Unconventional Memory to Preserve the Capacity to Mount Protective CD8 Memory Responses to Pathogens
This week we profile a recent publication in PNAS from the laboratory of Dr. Jennifer Lund
(fourth from left) at the Fred Hutchinson Cancer Research Center.
Can you provide a brief overview of your lab’s current research focus?
The focus of the Lund lab is on elucidating the basic mechanisms of anti-viral immunity and mucosal immunity using both mouse models as well as human tissues. Current projects include defining the roles and modes of action of tissue-resident memory T cells and regulatory T cells during mucosal virus infection, identifying novel mucosal immune correlates of protection from HIV-1 infection, and discovering new genes involved in immune responses to flavivirus infection, including both Zika and West Nile viruses. Overall, we hope that our studies will lead to improved clinical interventions for virus infections of public health importance.
What is the significance of the findings in this publication?
T cell-mediated immune memory provides the host with the capacity to rapidly and efficiently respond to pathogen re-encounter, often without symptoms or disease. In addition to conventional memory T cell responses that are pathogen-specific, there also exist a subset of unconventional memory T cells that share many of the characteristics of conventional memory T cells without the initiating requirement of cognate antigen recognition. Here, we demonstrate a mechanism whereby regulatory T cells limit the expansion of these unconventional memory T cells in order to preserve a host’s capacity to mount a memory CD8 T cell response that remains protective upon pathogen re-encounter.
What are the next steps for this research?
Our study demonstrates a critical role for regulatory T cells (Treg) in regulating both IL-15 trans-presentation as well as unconventional memory T cell development at least in part through CTLA-4 and b1-integrin. Thus, we believe that our findings have critical implications for Treg-directed therapeutics such as CLTA-4 and VLA-4 blockades (b1-integrin is part of the VLA-4 heterodimer), as there is potential for secondary long-term effects on the compositional dynamics of the host CD8+ T cell population. Thus, examination of how these therapeutic blockade strategies affect virtual memory T cell frequency and function, as well as how these therapies affect protective memory responses to infections is warranted.
This research was funded by:
This work was funded through R01 grants from the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH).