Analyses of thymic abnormalities in autoimmune-prone (NZW x BXSB) F1 mice.

Thymic abnormalities of autoimmune-prone (NZW x BXSB)F1 mice are investigated. After the onset of autoimmune diseases, severe thymic atrophy is observed. The atrophied thymus shows lower CD4+ CD8+ T cell and higher CD4+CD8- or CD4-CD8+ T cell counts than aged-matched normal strains or other autoimmune-prone (NZB x NZW)F1(B/WF1) mice; even at the age of 40 weeks, B/WF1 mice have a large number of double-positive cells and a small number of single-positive cells. Thymocytes in the atrophic thymus of (NZW x BXSB)F1 mice respond better than normal mice to T cell-mitogens (PHA and ConA). In addition, the single-positive T cells are J-11d-negative. These findings indicate that the atrophic thymus includes mature T cells and a large number of plasma cells and B cells; it therefore responds well to lipopolysaccharides. Experiments in reciprocal transplantation of the thymus and bone marrow between (NZW x BXSB)F1 and normal mice show that the thymic abnormalities are due to defects of the hemopoietic stem cells (HSCs) rather than either intrinsic abnormalities in the thymus or extrinsic abnormalities such as anti-thymus antibodies. It should be noted that the atrophic thymus recovers after transplantation of normal bone marrow cells; the atrophic thymus still has the capacity to induce the differentiation of normal T cells (including double-positive T cells) if normal HSCs are introduced.