Maternal autoimmune disease influences self-tolerance in offspring: the role of suppressor cells and materno-foetal cell traffic.
Autoimmune haemolytic anaemia (AIHA) was induced in normal strain (CBA/Ca/T6) mice by repeated intraperitoneal injection of rat red blood cells (RRBC). Antibody production to cross-reactive antigens on mouse red blood cells (MRBC) and foreign antigens on RRBC was measured by the direct antiglobulin test (DGAT) and serum haemagglutination, respectively. RRBC primed female or male mice and sheep red blood cell (SRBC) primed controls were mated with naive partners and their progeny immunized with RRBC in adult life. The offspring of mothers but not fathers with active autoimmune disease showed a significant reduction in antibody response to self (MRBC) antigens, whereas the response to non-self (RRBC) was unaffected. Transfer of 30 X 10(6) spleen cells from the progeny of RRBC primed mothers into non-irradiated normal recipients resulted in selective suppression of the anti-self response following challenge with RRBC, provided that the cell donors had been boosted with RRBC 7-10 days before the transfer was performed. Thus the progeny of mothers with AIHA possessed self-reactive memory suppressor cells (Ts) shown previously to belong to the Thy-1+ I-J+ Ly-2+ T cell subset in this model. To test whether the Ts were of maternal or foetal origin the suppressor assay was repeated with spleen cells from the F1 offspring of RRBC primed B10.A(3R) (I-Jb) mothers and normal CBA(I-Jk) fathers. Pretreatment with anti-I-Jb serum plus complement completely abrogated suppression on adoptive transfer but anti-I-Jk serum failed to do so, indicating that the Ts were derived from the mothers. These findings emphasize the potential importance of Ts in induction of self tolerance during early ontogeny.
Gibson
J
J
Clinical Immunology Research Centre, University of Sydney, NSW, Australia.
Basten
A
A
D000744:Anemia, Hemolytic, Autoimmune / Q000276:immunology; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D007112:Immunity, Maternally-Acquired; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D008815:Mice, Inbred Strains; D011247:Pregnancy; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*