Dysfunction of Ia-positive antigen-presenting cells in autoimmune mice

Antigen-presenting activity of spleen macrophages for T-cell activation was studied in vitro using autoimmune prone MRL/Mp-lpr/lpr (MRL/l) mice, and their normal counterparts, MRL/Mp-+/+ (MRL/n) mice. In vitro induction of trinitrophenyl (TNP)-specific proliferative T-cell response in lymph node lymphocytes from picryl chloride-painted mice was markedly impaired in MRL/l mice. The presenting activity of TNP-hapten by spleen macrophages for proliferative T cells was also impaired in MRL/l mice. The impairment of both T-cell and antigen-presenting macrophage activities was marked in older MRL/l mice, but not in younger ones. The impaired antigen-presenting activity of macrophages was not due to the development of suppressor macrophages. In accordance with the impaired antigen-presenting activity of macrophages the population of Ia-positive cells in spleen macrophages and the production of interleukin 1 by spleen macrophages were also reduced in older MRL/l mice. These results suggest that Ia-positive macrophages are impaired in autoimmune prone mice and that the dysfunction of Ia-positive macrophages plays an important role in the pathogenesis of autoimmune diseases.