Indexation as a novel mechanism of lymphocyte homeostasis: the number of CD4+CD25+ regulatory T cells is indexed to the number of IL-2-producing cells.
To fulfill its mission, the immune system must maintain a complete set of different cellular subpopulations that play specific roles in immune responses. We have investigated the mechanisms regulating CD4+CD25+ regulatory T (Treg) cell homeostasis. We show that the expression of the high-affinity IL-2Ralpha endows these cells with the capacity to explore the IL-2 resource, ensuring their presence while keeping their number tied to the number of CD4+ T cells that produce IL-2. We show that such a homeostatic mechanism allows the increased expansion of T cells without causing disease. The indexing of Treg cells to the number of activated IL-2-producing cells may constitute a feedback mechanism that controls T cell expansion during immune responses, thus preventing autoimmune or lymphoproliferative diseases. The present study highlights that maintenance of proportions between different lymphocyte subsets may also be critical for the immune system and are under strict homeostatic control.
Almeida
Afonso R M
AR
Lymphocyte Population Biology Unit, Unité de Recherche Associée, Centre National de la Recherche Scientifique, Institut Pasteur, 28 Rue du Dr. Roux, 75015 Paris, France.
Zaragoza
Bruno
B
Freitas
Antonio A
AA
D019264:Adoptive Transfer; D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D006706:Homeostasis / Q000276:immunology*; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000637:transplantation
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2