19 Jun 2020
New understanding of gamma delta T cells to aid development of more effective immune-based therapies
This week, Dr Jennifer Juno, a postdoctoral researcher from Professor Stephen Kent’s lab published an exciting piece of research in Cell Reports this week, looking at the role of gamma delta T cells, part of the family of ‘unconventional T cells’ in the immune system.
Here, Dr Juno explains what her and the research team identified.
Gamma delta T cells are part of the family of ‘unconventional T cells’ – T cells that share characteristics of many different types of immune cells.
In many ways, gamma delta T cells are a ‘jack-of-all-trades’: they have the ability to find and kill cells that are infected by viruses or bacteria, as well as tumour cells, they can secrete a wide range of immune signalling proteins, they provide help to other immune cells, and they travel throughout the circulation to multiple tissues.
The unique properties of gamma delta T cells therefore make them exciting candidates for immunotherapies to treat both infectious diseases and various types of cancer.
Over the course of our lifetime, our gamma delta T cells mature and change in response to infections or other immune challenges.
In some people, you can find very specialised cells that are potent killers, able to easily eliminate infected target cells. In other people, their gamma delta cells express key receptors that allow them to quickly move to inflamed tissues.
While this diversity is important, it can also act as a barrier to understanding how we best harness these cells to improve human health.
In this study, we identified a population of gamma delta T cells, found in nearly all adults, that maintains similar features to the gamma delta T cells present at birth.
These cells, defined by their expression of a molecule called CD26, are highly similar to other unconventional T cell populations, despite the fact that they respond to very different stimuli.
Importantly, we also found that stimulating these cells with an immune signalling molecule (IL-23) causes them to mature and become more cytotoxic, or able to kill target cells.
In some infections, such as HIV, these CD26-expressing gamma delta cells are depleted and never recover, likely contributing to the persistent immune dysfunction that can occur in some patients.
We hope that this new understanding of the role for IL-23 and CD26 in gamma delta T cell maturation will improve our ability to manipulate these cells and develop more effective immune-based therapies to treat infectious diseases or hard-to-treat cancers.