ABSTRACT
Interleukin-2 (IL-2)-deficient (IL-2-/-) mice develop anemia and colonic inflammatory bowel disease. To elucidate the mechanism of this disease, we have bred IL-2-/- mice to two strains of immunodeficient mice, RAG-2-deficient (RAG-2-/-, lacking B and T cells) and JH-deficient mice (JH-/-, lacking B cells). IL-2-/-, RAG-2-/- double-mutant mice are disease free, while IL-2-/-, JH-/- double-mutant mice succumb to bowel disease at the same rate as IL-2-/- littermates. IL-2-/-, JH-/- mice do not, however, succumb to anemia. Thus, spontaneous intestinal inflammation in IL-2-/- mice requires mature T cells, not B cells, while anemia is dependent on B cells.
Subject(s)
Autoimmune Diseases/immunology , B-Lymphocytes/immunology , DNA-Binding Proteins , Inflammatory Bowel Diseases/immunology , Interleukin-2/deficiency , T-Lymphocytes/immunology , Anemia, Hemolytic, Autoimmune/etiology , Anemia, Hemolytic, Autoimmune/immunology , Animals , Autoantibodies/analysis , Autoimmune Diseases/etiology , Autoimmune Diseases/pathology , Colon/pathology , Immunoglobulin Heavy Chains/genetics , Immunoglobulin J-Chains/genetics , Immunologic Deficiency Syndromes/complications , Immunologic Deficiency Syndromes/genetics , Inflammatory Bowel Diseases/etiology , Inflammatory Bowel Diseases/pathology , Interleukin-2/genetics , Mice , Mice, Knockout , Mice, Transgenic , Models, Immunological , Opportunistic Infections/complications , Proteins/genetics , Specific Pathogen-Free OrganismsABSTRACT
The bclx gene has been shown to regulate programmed cell death in vitro. We now show that Bclx expression increases dramatically when T cells differentiate from CD4- CD8- (double negative) thymocytes to CD4+ CD8+ [double positive (DP)] thymocytes. In contrast single-positive (SP) thymocytes express negligible amounts of Bclx protein. This expression pattern contrasts with that of Bcl2, which is present in double-negative thymocytes, down-regulated in DP thymocytes, and reinduced upon maturation to SP thymocytes. Elimination of Bclx by gene targeting dramatically shortens the survival of DP thymocytes but not the survival of SP thymocytes or peripheral SP T cells. These data suggest that the induction of Bclx during thymic maturation plays a critical role in regulating the length of time DP thymocytes survive in the absence of selection.
