Processes of Homeostatic Proliferation in the Pathogenesis of Autoimmune Glomerulonephritis Induced by Chronic Graft-Versus-Host Reaction

Abstract

Lymphopenia developing at the early stage of chronic graft-versus-host reaction is associated with increased content of IL-7 in the peripheral blood and leads to an increase of the CD4(+)and CD8(+)cell subpopulations in the spleen of the recipient. After 3 months, some animals develop autoimmune glomerulonephritis (lupus recipients). High levels of IL-7 and T-cells with the memory cell phenotype (CD4(+)CD45RB(low)and CD8(+)CD45RB(low)) persist in these animals, in contrast to nonlupus recipients without signs of autoimmune disease. This can attest to the involvement of homeostatic proliferation processes in the formation of autoimmune disease in this model.

The Experimental Model of the Autoimmune Glomerulonephritis Induced by the Chronic Graft versus Host Reaction

“…It has been shown the significantly increased level of endogenous splenic IL-7 mRNA in irradiated recipients with acute GVHR (Gendelman et al, 2004). The content of IL-7 in the peripheral blood of recipients with chronic GVHR sharply increases during the early period (25.5 pg/ml) and remains high within 3 months after induction of GVHD in lupus recipients (6.5 pg/ml) in comparison with control animals (lower the verge of method) and nonlupus recipients (lower the verge of method) (Goiman et al, 2010).…”

“…This decrease persists throughout the first two weeks and then is replaced by lymphocytosis followed by normalization of lymphocyte count in the peripheral blood against the background of developing splenomegaly (Tkachev et al, 2006). Hence it has been studied the possible involvement of homeostatic proliferation in the development of autoimmune disease -glomerulonephritis in this model (Goiman et al, 2010). An obligatory condition for homeostatic proliferation of naive and memory CD4 + T-cell is high concentration of IL-7 (Schluns et al, 2000;Boyman et al, 2008).…”