title: IL-2 and IL-7 determine the homeostatic balance between the regulatory and conventional CD4+ T cell compartments during peripheral T cell reconstitution.
abstract: Work over the last decades has led to the identification of the factors that influence the survival and homeostasis of conventional T cells. IL-7 and TCR signaling promote the survival of naive CD4(+) and CD8(+) T cells in lymphoreplete mice and their proliferation in a lymphopenic environment, whereas survival and homeostatic proliferation of memory CD4(+) and CD8(+) T cells crucially depend on a combination of IL-7 and IL-15. In contrast, there is little information regarding the factors driving the proliferation of regulatory CD4(+) T cells in response to lymphopenia. In this study, we investigated whether regulatory CD4(+) T cell proliferation in response to lymphopenia was guided by classical homeostatic resources, such as IL-2, IL-7, or TCR-MHC interactions. Altogether, our data suggest that, although homeostatic proliferation of conventional naive CD4(+) T cells is closely related to IL-7 levels, the proliferation of regulatory CD4(+) T cells in response to lymphopenia appears to be primarily controlled by IL-2. The capacity of IL-7 to augment conventional T cell proliferation with minimal concomitant regulatory T cell expansion may be clinically exploitable in the treatment of patients with lymphopenia, especially in the case of chronic viral diseases or cancer immunotherapy.
authors.affiliation: Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Cochin Hospital, 75014 Paris, France.
authors.forename: Armelle
authors.initials: A
authors.lastname: Le Campion
authors.forename: Arnaud
authors.initials: A
authors.lastname: Pommier
authors.forename: Arnaud
authors.initials: A
authors.lastname: Delpoux
authors.forename: Laurence
authors.initials: L
authors.lastname: Stouvenel
authors.forename: Cédric
authors.initials: C
authors.lastname: Auffray
authors.forename: Bruno
authors.initials: B
authors.lastname: Martin
authors.forename: Bruno
authors.initials: B
authors.lastname: Lucas
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D002451:Cell Compartmentation / Q000235:genetics / Q000276:immunology*; D002453:Cell Cycle / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D017930:Genes, Reporter; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D007376:Interleukin-2 / Q000502:physiology*; D015851:Interleukin-7 / Q000502:physiology*; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D007376:Interleukin-2; D015851:Interleukin-7