Lymphopenia-induced spontaneous T-cell proliferation as a cofactor for autoimmune disease development

作者：Le Campion Armelle; Gagnerault Marie Claude; Auffray Cedric; Becourt Chantal; Poitrasson Riviere Maud; Lallemand Eliette; Bienvenu Boris; Martin Bruno; Lepault Francoise; Lucas Bruno^*

来源：Blood, 2009, 114(9): 1784-1793.

DOI：10.1182/blood-2008-12-192120

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. (Blood. 2009;114: 1784-1793)

• 出版日期2009-8-27