Critical Reviews™ in Immunology

Development and Functional Properties of Thymic and Extrathymic T Lymphocytes

SINOPSIS

Although vertebrate hematopoiesis is known to occur in a variety of locations, the differentiation of T lymphocytes takes place only in the thymus. Conversely, the only known function of the thymus is to produce T lymphocytes. As thymic function progressively diminishes with age in all individuals, and decreased thymic capacity has been linked to an impaired resistance to infections and cancer, increasing thymic function and/or extrathymic T-cell development could thus play an important role in health management in elderly subjects. However, it is currently unclear why the thymus is essential for T-cell development and precisely what is necessary to make a functional T lymphopoietic organ. In this review, we shall discuss the current literature on the similarities and differences between thymic and extrathymic T cells. A major conclusion is that innate T cells can be generated extrathymically, but only the thymus can support the development of classic adaptive T cells. Functional differences between thymic and extrathymic T cells provide a rationale for conservation of the thymus as the sole primary T lymphoid organ. These differences also have implications for the management of thymus involution.