A dominant role for non-MHC gene effects in susceptibility to cyclosporin A (CsA)-induced autoimmunity.

Lethally irradiated LEW rats reconstituted with syngeneic bone marrow and given CsA for a 4-week period develop a graft-versus-host-like disease upon withdrawal of CsA. This T cell-mediated autoimmune disease is referred to as CsA-induced autoimmunity (CsA-AI). CsA-AI-susceptible LEW rats and resistant BN rats differ greatly in the composition of their peripheral T cell compartment.

Beta 2-microglobulin-dependent T cells are not necessary for alloantigen-induced Th2 responses after neonatal induction of lymphoid chimerism in mice.

We have analyzed the requirement for beta 2-microglobulin (beta 2m)-dependent T cells in the generation of allogeneic Th2 responses in vivo. A neonatal injection of semiallogeneic cells in BALB/c mice induces a state of chimerism that promotes the differentiation of donor-specific CD4+ T cells toward the Th2 phenotype. Polyclonal T-B cell interactions occur in this model between host Th2 and donor B cells, resulting in the production of IgE Abs.

Malignant neoplasms in cyclosporin A-induced autoimmunity (CyA-AI).

Lethally X-irradiated LEW rats reconstituted with syngeneic bone marrow and given low-dose Cyclosporine A (CyA) for 5 weeks develop, after withdrawal of CyA, symptoms of disease resembling graft-vs.-host disease (GVHD) as seen after allogeneic bone-marrow transplantation. Symptoms of disease may include acute dermatitis and chronic disease resembling scleroderma.

Macrophage infiltration at the neuromuscular junction does not contribute to AChR loss and age-related resistance to EAMG.

Aged rats resistant to acetylcholine receptor loss in passive transfer experimental autoimmune myasthenia gravis (EAMG) do not reveal infiltrating macrophages at the neuromuscular junction (NMJ) as observed in susceptible rats. It was investigated whether this age-related resistance is due to impaired macrophage function in these aged rats. Reconstitution of aged rats with bone marrow from young donors did not lead to macrophage infiltration, nor did it abolish resistance to EAMG.