Teaching immune tolerance

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 (T_reg) 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 T_reg 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 T_reg 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 T_reg 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 T_reg 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.