Homeostatic functions of tissue-homing memory T helper cells

Two hallmarks of adaptive T lymphocytes are their ability to respond in a ‘specific’ manner to invading pathogens through a highly diverse T cell antigen receptor (TCR), and their ability to provide long-term protection to said pathogen, called ‘memory’.

Memory T cells can enter the bloodstream, but these cells often end up occupying niches in the body that are unrelated to their initial antigenic trigger.

What do they do between the time they first see a pathogen and the following encounter, which may come years later or not at all? What factors are important for their maintenance in these tissue niches? And do they play meaningful roles in regulating our health independently of direct antigen-specific signals?

In this proposal, we focus on a subset of T lymphocytes called T helper cells, which secrete cytokines that are known to impact on all cell types in the body.

We will determine how T helper cells activated by one infection colonize distal tissues at the clonal level, determine the factors required for their survival, and pinpoint the contacts they make with stromal cells in tissues including the lung and skin.

Ultimately, we will determine how these tissue-homing memory T helper cells come to affect the function of our organs and study their impact on downstream responses to allergens and in wound healing responses.

In all, this project explores a modality of T cell function that has been neglected and aims to bring to light its importance in human health.