JCSMR 2016 Fenner Medal Seminar - Thymic T regulatory precursor formation is compartmentalised to a late CCR7+ Helios+ wave of negative selection

Dr Daniel Hu

Highly self-reactive T cells within the thymus undergo apoptosis when they encounter their cognate antigens, and so are “negatively selected” from the conventional T cell fate. This process occurs at both the early CCR7– cortical and the late CCR7+ medullary stage, meaning cells that undergo cortical apoptosis will not enter the medulla. Some self-reactive CCR7+ CD4SP cells undergo an alternative “agonist selection” fate and upregulate Foxp3, differentiating into immunosuppressive regulatory T cells. The IL-2 receptor CD25 and the transcription factor Helios are expressed on cells that receive a strong TCR signal. Conventional Treg precursors can be defined by CD25 expression. However, Helios expression can also distinguish Treg precursors that upregulate Foxp3 independent of CD25 expression. Therefore, a combination of Helios and other Treg-associated markers can be used to define a population of CD4SP thymocytes primed to upregulate Foxp3.

Dr Daniel Hu graduated with an Honours degree in 2009 working with Professor Frances Shannon and Dr Kristine Hardy on the role of the NF-κB molecule c-Rel on regulatory T cell development in the thymus. In 2015 he completed a PhD with Professor Christopher Goodnow and Dr Stephen Daley, working on the role of thymic Treg development, as well as the characterisation of an ENU mutation in Rasgrp1 that causes autoimmune disease. He has recently completed a postdoctoral fellowship with Professor Shimon Sakaguchi, working on the role of Helios as a Treg precursor marker, as well as the functional role of Helios.