last updated April 2013
Teaching immune tolerance
A specific subset of immune cells in the thymus facilitates the elimination and control of dangerous autoreactive lymphocytes
Researchers in Australia and the USA have shown that dendritic cells (DCs) are needed for efficient purging of autoreactive T lymphocytes and for the generation of regulatory T (Treg) lymphocytes. Impairment of either process can result in catastrophic autoimmunity.
Each T lymphocyte recognizes a limited set of protein fragments, or peptides. Within the thymus, several cell types ‘present’ a repertoire of self peptides to developing T cells, or thymocytes. Thymocytes that bind strongly to self peptides — and thus are autoreactive — will be instructed to die or converted into protective Treg cells.
The group, led by Li Wu at the Walter and Eliza Hall Institute of Medical Research, investigated the role of thymic DCs — one type of peptide ‘presenting’ cell — in thymocyte deletion and Treg cell generation.
Using bone marrow transplantation techniques, the researchers generated mice wherein thymic DCs are unable to present peptides. These mice showed inefficient thymocyte deletion and contained fewer Treg cells.
More detailed examination of distinct DC subpopulations revealed that the SIRPα+ type of thymic DCs — which enter the thymus from the blood — more efficiently induce Treg cell generation than SIRPα– thymic DCs.
Thus, by ‘importing’ peptides from the blood into the thymus, SIRPα+ DCs may facilitate exposure of thymocytes to a wider array of self proteins.