MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II EXPRESSION BY INTRINSIC RENAL-CELLS IS REQUIRED FOR CRESCENTIC GLOMERULONEPHRITIS

The requirement for major histocompatibility complex class II (MHC II) to initiate immune renal injury was studied in a murine model of CD4 T cell-dependent crescentic glomerulonephritis (GN). C57BL/6 (MHC II/+) mice developed crescentic GN with glomerular CD4+ T cell infiltrat ion and renal injury, in response to a nephritogenic antigen (sheep gl obulin) planted on their glomerular basement membrane. MHC II-deficien t C57BL/6 mice (MHC II-/-) did not develop crescentic GN, CD4+ T cell infiltration, or injury, indicating that this form of immune glomerula r injury is MHC II dependent. The requirement for MHC II expression by intrinsic renal cells was studied in chimeric mice, which expressed M HC II on bone marrow-derived cells and in the thymus, but not in the k idneys. These chimeric mice had normal T and B cell populations and MH C II expression in their spleens and lymph nodes and developed an immu ne response to systemically and cutaneously administered sheep globuli n. However, they did not develop crescentic GN, CD4+ T cell infiltrati on, or renal injury in response to the sheep globulin planted in their glomeruli. These studies demonstrate that interaction of CD4+ T cells with intrinsic renal cells expressing MHC II is required for developm ent of cell-mediated immune renal injury.