In normal mice, not all T-lineage cells are generated and selected in the thymus; an
alternative, extrathymic, development pathway exists. Extrathymic T cells are rare in the
spleen and lymph nodes, but are abundant in some tissues, such as the gut. Here, Benedita
Rocha, Pierre Vassalli and Delphine Guy-Grand discuss the rules of selection of extrathymic
T cells, assess the possible role of these cells in the defence of epithelial integrity and their
potential role in autoimmune disease.