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

Eur J Immunol. 1995 Jan;25(1):238-44. doi: 10.1002/eji.1830250139.


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 alpha and beta subunits of the gastric H+/K+ ATPase. Transgenic mice, expressing the gastric H+/K+ ATPase beta-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 beta-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / immunology
  • Animals
  • Autoimmune Diseases / etiology
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / pathology
  • B-Lymphocytes / drug effects
  • Cyclophosphamide
  • Flow Cytometry
  • Gastritis / etiology
  • Gastritis / immunology*
  • Gastritis / pathology
  • H(+)-K(+)-Exchanging ATPase / immunology
  • Immunoblotting
  • Immunotherapy, Adoptive
  • Lymphopenia / chemically induced
  • Lymphopenia / complications
  • Lymphopenia / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred DBA
  • Mice, Transgenic
  • Organ Specificity / immunology
  • Spleen / cytology
  • T-Lymphocytes / drug effects
  • Thymectomy
  • Thymus Gland / physiology*


  • Cyclophosphamide
  • H(+)-K(+)-Exchanging ATPase