INTRATHYMIC INJECTION OF POLYNUCLEOSOMES DELAYS AUTOANTIBODY PRODUCTION IN BXSB MICE

T-cell dependent autoimmunization with nucleosomes appears to be an ea rly event in the induction of lupus anti-chromatin antibodies. We inve stigated this phenomenon by injecting H1-stripped chromatin polynucleo somes into the thymuses of BXSB male lupusprone mice. In comparison to uninjected controls, the production of IgG antichromatin, anti-native DNA, and anti-denatured DNA were significantly reduced among the inje cted animals for a period of 8 to 10 weeks. Peripheral T-cells from in trathymic (i.t.)-treated animals showed decreased proliferative respon ses to polynucleosomes compared to those from uninjected controls. Tre atment did not affect T-cell antigen receptor V beta profiles, excludi ng the possibility that results were due to superantigen-imposed delet ions, In situ staining using the TUNEL method demonstrated that genera tion and phagocytosis of apoptotic material in thymuses of unmanipulat ed BXSB mice were similar to normal controls, These findings show that polynucleosomes likely comprise the antigens for helper T-cell engage ment and induction of lupus-associated anti-chromatin antibodies. Bypa ssing the underlying defect of T-cell tolerance for polynucleosomal an tigens among BXSB mice, by i.t. administration of exogenous polynucleo somes, results in abrogation of autoantibody production. (C) 1996 Acad emic Press, Inc.