ORGAN-SPECIFIC AUTOIMMUNITY INDUCED BY ADULT THYMECTOMY AND CYCLOPHOSPHAMIDE-INDUCED LYMPHOPENIA

Autoimmune gastritis, a CD4(+) T cell-mediated organ-specific autoimmu ne disease, can be induced by thymectomy of neonatal, but not of older , BALB/c mice. Here we have shown that autoimmune gastritis can also b e induced in 6-8-week-old BALB/c mice by thymectomy combined with a si ngle dose of cyclophosphamide (300 mg/kg). This treatment reduced the numbers of splenic T and B cells approximately 25-fold. However, by 8 days after treatment, the number of splenic lymphocytes had returned t o normal adult levels. Approximately 50% of treated mice developed aut oimmune gastritis after 10-12 weeks. These mice had mononuclear cellul ar infiltrates within the gastric mucosa and serum autoantibodies to t he alpha and beta subunits of the gastric H+/K+ ATPase. Transgenic mic e, expressing the gastric H+/K+ ATPase beta-subunit in the thymus (Ald eruccio, F., Toh, B. H., Tan, S. S., Gleeson, P. A. and van Driel, I. R., J. Exp. Med. 1993. 178: 419), did not develop autoimmune gastritis after the adult thymectomy/cyclophosphamide treatment. Thus a T cell response to the H+/K+ ATPase beta-subunit is likely to be required for the onset of gastritis. These observations suggest that pathogenic au toreactive T cells exist in the periphery of normal adult mice and tha t autoimmunity can be induced by the activation of these autoreactive T cells following transient lymphopenia. Cyclophosphamide-treatment of adult mice without thymectomy did not induce autoimmune gastritis, su ggesting thymic regulation of these pathogenic T cells.