Peripheral regulatory T lymphocytes recirculating to the thymus suppress the development of their precursors.
Most T lymphocytes, including regulatory T cells (Treg cells), differentiate in the thymus. The age-dependent involution of this organ leads to decreasing production of T cells. Here we found that the output of new Treg cells from the thymus decreased substantially more than that of conventional T cells. Peripheral mouse and human Treg cells recirculated back to the thymus, where they constituted a large proportion of the pool of Treg cells and displayed an activated and differentiated phenotype. In the thymus, the recirculating cells exerted their regulatory function by inhibiting interleukin 2 (IL-2)-dependent de novo differentiation of Treg cells. Thus, Treg cell development is controlled by a negative feedback loop in which mature progeny cells return to the thymus and restrain development of precursors of Treg cells.
1] Institut National de la Santé et de la Recherche Médicale U1043, Toulouse, France. [2] Centre National de la Recherche Scientifique U5282, Toulouse, France. [3] Université de Toulouse, Université Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France.
Nicolas
N
Thiault
1] Institut National de la Santé et de la Recherche Médicale U1043, Toulouse, France. [2] Centre National de la Recherche Scientifique U5282, Toulouse, France. [3] Université de Toulouse, Université Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France.
Julie
J
Darrigues
1] Institut National de la Santé et de la Recherche Médicale U1043, Toulouse, France. [2] Centre National de la Recherche Scientifique U5282, Toulouse, France. [3] Université de Toulouse, Université Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France.
Véronique
V
Adoue
1] Institut National de la Santé et de la Recherche Médicale U1043, Toulouse, France. [2] Centre National de la Recherche Scientifique U5282, Toulouse, France. [3] Université de Toulouse, Université Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France. [4] Ecole Normale Supérieure de Lyon, Department of Biology, 69007 Lyon, France.
Marine
M
Gros
1] Institut National de la Santé et de la Recherche Médicale U1043, Toulouse, France. [2] Centre National de la Recherche Scientifique U5282, Toulouse, France. [3] Université de Toulouse, Université Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France.
Bénédicte
B
Binet
1] Institut National de la Santé et de la Recherche Médicale U1043, Toulouse, France. [2] Centre National de la Recherche Scientifique U5282, Toulouse, France. [3] Université de Toulouse, Université Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France.
Corine
C
Perals
Department of Pediatric Cardiology and Cardiovascular surgery, Children Hospital, University Hospital of Toulouse, Toulouse, France.
Bertrand
B
Leobon
1] Institut National de la Santé et de la Recherche Médicale U1043, Toulouse, France. [2] Centre National de la Recherche Scientifique U5282, Toulouse, France. [3] Université de Toulouse, Université Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France.
Nicolas
N
Fazilleau
1] Institut National de la Santé et de la Recherche Médicale U1043, Toulouse, France. [2] Centre National de la Recherche Scientifique U5282, Toulouse, France. [3] Université de Toulouse, Université Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France.
Olivier P
OP
Joffre
Department of Molecular and Cell Biology, Division of Immunology and Pathogenesis, University of California, Berkeley, California, USA.
Ellen A
EA
Robey
1] Institut National de la Santé et de la Recherche Médicale U1043, Toulouse, France. [2] Centre National de la Recherche Scientifique U5282, Toulouse, France. [3] Université de Toulouse, Université Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France.
Joost P M
JP
van Meerwijk
1] Institut National de la Santé et de la Recherche Médicale U1043, Toulouse, France. [2] Centre National de la Recherche Scientifique U5282, Toulouse, France. [3] Université de Toulouse, Université Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France.
Paola
P
Romagnoli
D000375:Aging / Q000276:immunology; D000818:Animals; D001775:Blood Circulation; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D002648:Child; D025461:Feedback, Physiological; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054504:Precursor Cells, T-Lymphoid / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D013950:Thymus Gland / Q000276:immunology*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2