Organ‐specific autoimmunity induced by adult thymectomy and cyclophosphamide‐induced lymphopenia

Autoimmune gastritis, a CD4⁺ T cell‐mediated organ‐specific autoimmune disease, can be induced by thymectomy of neonatal, but not of older, BALB/c mice. Here we have shown that autoimmune gastritis can also be induced in 6–8‐week‐old BALB/c mice by thymectomy combined with a single 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 to normal adult levels. Approximately 50% of treated mice developed autoimmune gastritis after 10–12 weeks. These mice had mononuclear cellular infiltrates within the gastric mucosa and serum autoantibodies to the α and β subunits of the gastric H⁺/K⁺ ATPase. Transgenic mice, expressing the gastric H⁺/K⁺ ATPase β‐subunit in the thymus (Alderuccio, 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 β‐subunit is likely to be required for the onset of gastritis. These observations suggest that pathogenic autoreactive T cells exist in the periphery of normal adult mice and that 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, suggesting thymic regulation of these pathogenic T cells.