CELL-FREE DNA IN THE BLOOD OF MICE WITH TH1- AND TH2-DEPENDENT VARIANTS OF CHRONIC GRAFT-VERSUS-HOST DISEASE

Abstract

According to generally accepted concepts today, the levels of extracellular DNA in patients with various pathologies differ significantly depending on the severity of their systemic inflammation. One of the factors directly related to the mechanisms of development of the inflammatory process is the predominance of Th1- or Th2-dependent immune responses during disease development. The aim of this work was to study the effect of Th1/Th2 balance on the level of extracellular DNA in the blood of experimental animals in a model system for the development of chronic graft-versus-host disease. Chronic GVHD was induced by transferring lymphoid cells from DBA mice to first-generation hybrid mice (C57Bl/6xDBA/2)F1. In one part of the experimental animals, the predominance of the Th1-dependent variant led to the development of a pronounced immunodeficiency state, while in another part of the mice, a Th2-dependent variant of this immunopathological process is manifested, ultimately resulting in the formation of immune complex glomerulonephritis. Cell-free DNA was measured at different time points in the development of chronic graft-versus-host disease. It was shown that in the group of mice, upon induction of cGVHD, an increase in the level of cfDNA in the blood plasma was observed already at early stages, while the concentration of cfDNA associated with the cell membrane remained unchanged. By the time of formation of clinical outcomes of cGVHD, in the case of the Th1-dependent variant, the concentrations of cfDNA do not differ from the corresponding values ​​in the group of animals with syngeneic transfer. The data obtained indicate that the dominance of Th1 lymphocyte activity does not lead to an increase in the level of cfDNA in the blood. In another group of animals, with a predominance of the immunopathological process occurring along the Th2-dependent pathway, a significant increase in the level of cfDNA in the blood is found, apparently due to the development of immune complex glomerulonephritis. Thus, the previous predominance of Th2 lymphocyte activity does not prevent the occurrence of nephritis, accompanied by an increase in the level of cfDNA.