Original Article

T Cell Homeostasis: Thymus Regeneration and Peripheral T Cell Restoration in Mice with a Reduced Fraction of Competent Precursors

Correspondence to: António A. Freitas, Lymphocyte Population Biology Unit, URA CNRS 1961, Institut Pasteur, 25 Rue du Dr. Roux, 75015 Paris, France. Tel:33-1-45-68-8552 Fax:33-1-45-68-8921 E-mail:afreitas{at}pasteur.fr.

We developed a novel experimental strategy to study T cell regeneration after bone marrow transplantation. We assessed the fraction of competent precursors required to repopulate the thymus and quantified the relationship between the size of the different T cell compartments during T cell maturation in the thymus. The contribution of the thymus to the establishment and maintenance of the peripheral T cell pools was also quantified. We found that the degree of thymus restoration is determined by the availability of competent precursors and that the number of double-positive thymus cells is not under homeostatic control. In contrast, the sizes of the peripheral CD4 and CD8 T cell pools are largely independent of the number of precursors and of the number of thymus cells. Peripheral "homeostatic" proliferation and increased export and/or survival of recent thymus emigrants compensate for reduced T cell production in the thymus. In spite of these reparatory processes, mice with a reduced number of mature T cells in the thymus have an increased probability of peripheral T cell deficiency, mainly in the naive compartment.

Key Words: CD4 T cells, CD8 T cells, homeostasis, thymus regeneration, thymus export

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