Submitted December 1, 2008
Accepted June 15, 2009
Lymphopenia-induced spontaneous T-cell proliferation as a cofactor for autoimmune disease development
Armelle Le Campion, Marie-Claude Gagnerault, Cedric Auffray, Chantal Becourt, Maud Poitrasson-Riviere, Eliette Lallemand, Boris Bienvenu, Bruno Martin, Francoise Lepault, and Bruno Lucas*
Institut Cochin, Universite Paris Descartes, CNRS UMR 8104, Cochin Hospital, Paris, France
INSERM U561, Saint-Vincent-de-Paul Hospital, Paris, France
INSERM U567, Cochin Hospital, Paris, France
* Corresponding author; email: bruno.lucas{at}inserm.fr.
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). Here, 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 NOD mice, differences in the ability of conventional and regulatory T cells to expand in response to lymphopenia led to an unbalance between these two 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.
