Garvan researchers overturn T cell “dogma”

Researchers from Sydney’s Garvan Institute have challenged the dominant view in immunology circles as to how a special type of immune cell, called a T follicular helper cell (Tfh), is generated.

The previous theory as to the origins of Tfh cells was so widespread that the Garvan researchers refer to is as the prevailing “dogma”.

The research, led by Dr Elissa Deenick, Dr Stuart Tangye and Dr Robert Brink from the Garvan Institute, will be published in the prestigious journal Immunity, and is sure to cause a stir in immunology circles.

“As they’re so central, it’s important for us to understand exactly how they work,” said Deenick, who has been working on this project for three years. “One of the muddiest areas of debate has been how they’re generated in the first place, and I believe our findings clarify that.”

There are many types of T cells and B cells that play a central role in the adaptive immune system and our ability to respond to a wide range of pathogens. One particular type of T cell, the T follicular helper cell, was only discovered in 2000, and there has been a slew of research in recent years exploring their function and origin.

The Tfh cell was found to play an important role in ‘priming’ B cells into producing antibodies to combat infection. They start off as T cells that express certain proteins and receptors on their surface which allow them to migrate to germinal centres, such as in the spleen and lymph nodes.

The cells also need to be activated by exposure to an antigen, and it was widely believed that another immune cell, dendritic cells, performed the role of delivering the antigen to activate them. They would then migrate to the germinal centres and B cells would issue a chemical signal that would turn them into Tfh cells.

This paper shows that this two-stage approach is not entirely accurate.

“Our work shows that the B cell doesn’t send any unique signal to the T cell to help it become a T follicular helper cell – but that dendritic cells can give the T cells all the signals that they need to make the change,” said Deenick.

“The important thing is that antigen needs to be given to a T cell, and that can come from a dendritic cell, a B cell, or any other source.”

So while it is possible for the T follicular helper cells to be primed by a B cell, it wasn’t the only way to activate them.

The team demonstrated this by circumventing the B cells and having other cells give the signal to the Tfh cell, thus showing there was an alternate pathway to the generation of the cells.

The finding could have implications for the way that vaccines are developed, said co-author on the paper, Dr Stuart Tangye.

“If you have a vaccine that has a broad response - so some people respond to it poorly and some respond to it well - it could be because the T cells are getting the wrong signal from the B cells. So instead of putting all our eggs in the B cell basket, we could find other ways to improve the chances to get the right responding T cell.”

The article will appear in the next issue of Immunity: DOI: 10.1016/j.immuni.2010.07.015.