Lymphopenia-induced spontaneous T-cell proliferation as a cofactor for autoimmune disease development.
Lymphopenia is thought to be a major cause of tolerance breakdown. In a lymphopenic environment, self-recognition events induce some T cells to expand strongly (a mechanism known as spontaneous proliferation). In this study, we show that in C57BL/6 mice, the repertoire resulting from lymphopenia-induced spontaneous CD4(+) T-cell proliferation included a proportion of regulatory T cells as large as that observed in a normal mouse, and no autoimmune disorder was observed. By contrast, in nonobese diabetic mice, differences in the ability of conventional and regulatory T cells to expand in response to lymphopenia led to an unbalance between these 2 T-cell compartments at the expense of regulatory T cells, resulting in the onset of autoimmune diseases. Notably, this accounted for the rapid transfer of diabetes with small numbers of BDC2.5 CD4(+) T cells. Thus, lymphopenia does not itself induce autoimmunity, but it should be considered as a cofactor for the development of autoimmune disorders.
Le Campion
Armelle
A
Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Cochin Hospital, Paris, France.
Gagnerault
Marie-Claude
MC
Auffray
Cédric
C
Bécourt
Chantal
C
Poitrasson-Rivière
Maud
M
Lallemand
Eliette
E
Bienvenu
Boris
B
Martin
Bruno
B
Lepault
Françoise
F
Lucas
Bruno
B
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D017252:CD3 Complex / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation; D049109:Cell Proliferation; D005434:Flow Cytometry / Q000379:methods; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008024:Ligands; D008231:Lymphopenia / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology
D017252:CD3 Complex; D008024:Ligands; D017493:Leukocyte Common Antigens