Immunologic abnormalities of mice bearing the gld mutation suggest a common pathway for murine nonmalignant lymphoproliferative disorders with autoimmunity

Abstract

Mice bearing the autosomal recessive mutation gld have been shown to develop massive lymphadenopathy, hypergammaglobulinemia, and autoantibodies and to die prematurely with interstitial pneumonitis. In this study, lymphocytes from C3H gld and C3H +/+ mice were examined for a variety of phenotypic and functional characteristics. Spleens and lymph nodes of mutant mice were expanded by an aberrant population of Ly-5(B220)+ surface immunoglobulin negative cells that were Thy-1+Ly-1+ or Thy-1-Ly-1+. Cells from both tissues of mutant mice older than 8 wk were impaired in their ability to proliferate in response to allogeneic stimuli, and supernatants of cells stimulated with concanavalin A contained significantly reduced levels of interleukin 2. Cytotoxic T-lymphocyte responses of spleen and lymph node cells from C3H gld mice were normal at all ages tested. These results are strikingly similar to those obtained with C3H mice homozygous for the nonallelic autosomal recessive mutation lpr. We suggest that the similarities between the syndromes induced by these two mutations may reflect alterations in different enzymes that act in a common metabolic pathway of major importance to the differentiation and function of T cells.