%0 Journal Article
%T Systemic Autoimmunity and Lymphoproliferation Are Associated with Excess IL-7 and Inhibited by IL-7R¦Á Blockade
%A Rosana Gonzalez-Quintial
%A Brian R. Lawson
%A John C. Scatizzi
%A Joseph Craft
%A Dwight H. Kono
%A Roberto Baccala
%A Argyrios N. Theofilopoulos
%J PLOS ONE
%D 2011
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0027528
%X Lupus is characterized by disturbances in lymphocyte homeostasis, as demonstrated by the marked accumulation of activated/memory T cells. Here, we provide evidence that proliferation of the CD8+ precursors for the accumulating CD4¨CCD8¨C T cells in MRL-Faslpr lupus-predisposed mice is, in part, driven by commensal antigens. The ensuing lymphadenopathy is associated with increased production of IL-7 due to expansion of fibroblastic reticular cells, the primary source of this cytokine. The excess IL-7 is not, however, consumed by CD4¨CCD8¨C T cells due to permanent down-regulation of IL-7R¦Á (CD127), but instead supports proliferation of autoreactive T cells and progression of autoimmunity. Accordingly, IL-7R blockade reduced T cell activation and autoimmune manifestations even when applied at advanced disease stage. These findings indicate that an imbalance favoring production over consumption of IL-7 may contribute to systemic autoimmunity, and correction of this imbalance may be a novel therapeutic approach in lymphoproliferative and autoimmune syndromes.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0027528