Immunopathogenesis of autoimmune tubulointerstitial nephritis. II. Role of an immune response gene linked to the major histocompatibility complex

Abstract

Immunization of strain XIII guinea pigs with rabbit renal tubular basement membranes (TBM) in CFA consistently results in severe autoimmune tubulointerstitial nephritis (TN). Strain II guinea pigs similarly immunized do not develop this disease. F1 guinea pigs were found to be intermediate between inbred strain II and XIII animals with regard to extent of autoimmune TN and anti-TBM antibody production. The F1 X II backcrosses segregated into two groups with regard to antibody production and disease extent. Those backcrosses tissue typed as II+, XIII+ were similar to the F1 guinea pigs. Those backcrosses typed as II+,II+ demonstrated little disease and low anti-TBM titers similar to the inbred strain II animals. F1 X XIII backcrossed guinea pigs segregated into II+,XIII+ or XIII+,XIII+ subgroups on the basis of lymph node typing. The II+, XIII+ backcross animals resembled F1 guinea pigs with respect to anti-TBM response and disease extent; whereas the XIII+, XIII+ backcrosses developed severe disease and high anti-TBM titers as observed in the inbred strain XIII animals. These experiments suggest that susceptibility to autoimmune TN in the guinea pig is linked to the strain XIII major histocompatibility complex and that an immune response gene governing this susceptibility may be inherited as a single dominant or co-dominant trait.