IMMUNOPATHOLOGY OF INTERLEUKIN (IL)2-DEFICIENT MICE - THYMUS DEPENDENCE AND SUPPRESSION BY THYMUS-DEPENDENT CELLS WITH AN INTACT IL-2 GENE

Interleukin (IL) 2-deficient mice develop a fatal immunopathology char acterized by lymphadenopathy, splenomegaly, T cell infiltration of the bone marrow, loss of B cells, anemia, and inflammation of the gut. Th e thymus dependence of these disease symptoms was tested by introducin g the IL-2 mutation into athymic mice. With the exception of an increa se in CD8(+) intrahepatic alpha/beta T cells, IL-2 deficiency had no d etectable effect on leukocyte composition or health of athymic mice, i ndicating a key role for thymus-derived T cells in the initiation of d isease and demonstrating that B cell development and survival are inde pendent of IL-2. In adoptive transfer studies, lymph node and spleen c ells from euthymic IL-2-deficient mice induced disease in athymic mice with an intact IL-2 gene, suggesting that thymus-independent IL-2-exp ressing cells are unable to control the development of immune patholog y. Both IL-2(+) and IL-2(-/-) bone marrow cells repopulated the thymus and the peripheral T cell compartment of the recombination activator gene 2-deficient recipients, and chimeras that had received IL-2-defic ient bone marrow developed immune pathology. Disease development was, however, fully or at least partially prevented when 30% of the bone ma rrow inoculum was derived from mice able to express IL-2. These result s demonstrate that the IL-2 deficiency syndrome depends on the intrath ymic differentiation of T cells carrying the IL-2 mutation, and that t he abnormal activation of IL-2-deficient lymphocytes can be controlled by thymus-derived but not thymus-independent lymphocytes.