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Organ-specific autoimmunity induced by adult thymectomy and cyclophosphamide-induced lymphopenia.
Eur J Immunol 1995; 25(1):238-44EJ

Abstract

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.

Authors+Show Affiliations

Department of Pathology and Immunology, Monash University Medical School, Alfred Hospital, Melbourne, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7843236

Citation

Barrett, S P., et al. "Organ-specific Autoimmunity Induced By Adult Thymectomy and Cyclophosphamide-induced Lymphopenia." European Journal of Immunology, vol. 25, no. 1, 1995, pp. 238-44.
Barrett SP, Toh BH, Alderuccio F, et al. Organ-specific autoimmunity induced by adult thymectomy and cyclophosphamide-induced lymphopenia. Eur J Immunol. 1995;25(1):238-44.
Barrett, S. P., Toh, B. H., Alderuccio, F., van Driel, I. R., & Gleeson, P. A. (1995). Organ-specific autoimmunity induced by adult thymectomy and cyclophosphamide-induced lymphopenia. European Journal of Immunology, 25(1), pp. 238-44.
Barrett SP, et al. Organ-specific Autoimmunity Induced By Adult Thymectomy and Cyclophosphamide-induced Lymphopenia. Eur J Immunol. 1995;25(1):238-44. PubMed PMID: 7843236.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Organ-specific autoimmunity induced by adult thymectomy and cyclophosphamide-induced lymphopenia. AU - Barrett,S P, AU - Toh,B H, AU - Alderuccio,F, AU - van Driel,I R, AU - Gleeson,P A, PY - 1995/1/1/pubmed PY - 1995/1/1/medline PY - 1995/1/1/entrez SP - 238 EP - 44 JF - European journal of immunology JO - Eur. J. Immunol. VL - 25 IS - 1 N2 - 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. SN - 0014-2980 UR - https://www.unboundmedicine.com/medline/citation/7843236/Organ_specific_autoimmunity_induced_by_adult_thymectomy_and_cyclophosphamide_induced_lymphopenia_ L2 - https://doi.org/10.1002/eji.1830250139 DB - PRIME DP - Unbound Medicine ER -