Сell-free DNA in blood of mice with Th1- and Th2-dependent variants of chronic graft-versus-host disease

According to current concepts, the levels of extracellular DNA (cfDNA) in patients with various disorders may significantly depend on the severity of their systemic inflammation. Predominance of Th1- or Th2-dependent immune responses during the disease development is directly related to the mechanisms of emerging inflammatory process. The aim of this work was to study the effect of Th1/Th2 balance on the cfDNA levels in blood of experimental animals using an animal model chronic graft-versus-host disease (cGVHD). This condition was induced by transferring lymphoid cells from DBA mice to the first-generation hybrid mice (C57Bl/6xDBA/2)F1. In a subgroup of animals, the predominance of Th1-dependent variant led to a pronounced immunodeficiency state. In other subgroup, this immunological disorder manifested as a Th2-dependent variant, ultimately resulting in the formation of immune complex glomerulonephritis. Cell-free DNA (cfDNA) was measured at different time points during the development of cGVHD. We have shown that in a subgroup of mice, an increased level of plasma cfDNA was observed as soon as at early stages upon induction of cGVHD, whereas the contents of cell membrane-associated cfDNA remained unchanged. By the time of registering clinical outcomes of cGVHD, in the case of the Th1-dependent variant, the concentrations of cfDNA do not differ from appropriate values in the animals subjected to syngeneic transplant. The data obtained suggest that the dominance of Th1 lymphocyte activity does not lead to increased cfDNA level in murine blood. In another group of animals, with a predominance of the immunopathology developing via Th2-dependent pathway, a significantly increased level of cfDNA in blood is found, apparently, due to development of immune complex-associated glomerulonephritis. Thus, the preceding dominance of Th2 lymphocyte activity does not prevent the occurrence of nephritis, accompanied by increased cfDNA levels.