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Blood, 27 August 2009, Vol. 114, No. 9, pp. 1784-1793.
Prepublished online as a Blood First Edition Paper on June 26, 2009; DOI 10.1182/blood-2008-12-192120.


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IMMUNOBIOLOGY

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

Armelle Le Campion1,2, Marie-Claude Gagnerault3, Cédric Auffray1,2, Chantal Bécourt3, Maud Poitrasson-Rivière1,2, Eliette Lallemand1,2, Boris Bienvenu1,2, Bruno Martin1,2, Françoise Lepault1,2, and Bruno Lucas1,2

1 Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Cochin Hospital, Paris; 2 Inserm Unité 567, Cochin Hospital, Paris; and 3 Inserm Unité 561, Saint-Vincent-de-Paul Hospital, Paris, France

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.


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