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Pathogenesis of post-thymectomy autoimmunity. Role of syngeneic MLR-reactive T cells.
J Immunol 1995; 154(12):6602-11JI

Abstract

Thymectomy of 3-day-old mice results in the development of multi-organ-specific autoimmune diseases. The disease process is mediated by CD4+ T cells and is characterized by an inflammatory infiltrate in the affected organ(s) and the presence of autoantibodies. Our analysis of the phenotype of the CD4+ T cells that remain in the 3-day thymectomized animal revealed that the majority (approximately 80%) of the CD4+ lymph node cells express an activated (MEL-14low) phenotype and a smaller percentage expressed the T cell activation Ag CD69 and IL-2R alpha-chain. Thymectomized animals also had an increase in the frequency of mitogen-induced CD4+ IL-4 producers and significantly higher levels of total serum IgG. Functional studies demonstrated that lymph node T cells from 3-day thymectomized mice had an enhanced response in the syngeneic MLR and appeared to preferentially respond to syngeneic dendritic cells. To determine whether the syngeneic MLR-reactive T cells were involved in the pathogenesis of the organ-specific disease, we developed a model that mimicked the 3dTx model by grafting neonatal thymi to adult nu/nu recipients followed by removal of the thymus graft on day 3 or 4. When compared with mice transplanted with an untreated thymus, nu/nu mice transplanted with adult APC-containing thymi demonstrated a decrease in the incidence and severity of gastritis, a marked decrease in the titer of anti-parietal cell Ab, and a decrease in total serum IgG. Thus, intrathymic tolerization to complexes of self-peptides and MHC class II on adult APC prevents organ-specific autoimmune disease.

Authors+Show Affiliations

Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

7759894

Citation

Bonomo, A, et al. "Pathogenesis of Post-thymectomy Autoimmunity. Role of Syngeneic MLR-reactive T Cells." Journal of Immunology (Baltimore, Md. : 1950), vol. 154, no. 12, 1995, pp. 6602-11.
Bonomo A, Kehn PJ, Payer E, et al. Pathogenesis of post-thymectomy autoimmunity. Role of syngeneic MLR-reactive T cells. J Immunol. 1995;154(12):6602-11.
Bonomo, A., Kehn, P. J., Payer, E., Rizzo, L., Cheever, A. W., & Shevach, E. M. (1995). Pathogenesis of post-thymectomy autoimmunity. Role of syngeneic MLR-reactive T cells. Journal of Immunology (Baltimore, Md. : 1950), 154(12), pp. 6602-11.
Bonomo A, et al. Pathogenesis of Post-thymectomy Autoimmunity. Role of Syngeneic MLR-reactive T Cells. J Immunol. 1995 Jun 15;154(12):6602-11. PubMed PMID: 7759894.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pathogenesis of post-thymectomy autoimmunity. Role of syngeneic MLR-reactive T cells. AU - Bonomo,A, AU - Kehn,P J, AU - Payer,E, AU - Rizzo,L, AU - Cheever,A W, AU - Shevach,E M, PY - 1995/6/15/pubmed PY - 1995/6/15/medline PY - 1995/6/15/entrez SP - 6602 EP - 11 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 154 IS - 12 N2 - Thymectomy of 3-day-old mice results in the development of multi-organ-specific autoimmune diseases. The disease process is mediated by CD4+ T cells and is characterized by an inflammatory infiltrate in the affected organ(s) and the presence of autoantibodies. Our analysis of the phenotype of the CD4+ T cells that remain in the 3-day thymectomized animal revealed that the majority (approximately 80%) of the CD4+ lymph node cells express an activated (MEL-14low) phenotype and a smaller percentage expressed the T cell activation Ag CD69 and IL-2R alpha-chain. Thymectomized animals also had an increase in the frequency of mitogen-induced CD4+ IL-4 producers and significantly higher levels of total serum IgG. Functional studies demonstrated that lymph node T cells from 3-day thymectomized mice had an enhanced response in the syngeneic MLR and appeared to preferentially respond to syngeneic dendritic cells. To determine whether the syngeneic MLR-reactive T cells were involved in the pathogenesis of the organ-specific disease, we developed a model that mimicked the 3dTx model by grafting neonatal thymi to adult nu/nu recipients followed by removal of the thymus graft on day 3 or 4. When compared with mice transplanted with an untreated thymus, nu/nu mice transplanted with adult APC-containing thymi demonstrated a decrease in the incidence and severity of gastritis, a marked decrease in the titer of anti-parietal cell Ab, and a decrease in total serum IgG. Thus, intrathymic tolerization to complexes of self-peptides and MHC class II on adult APC prevents organ-specific autoimmune disease. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/7759894/Pathogenesis_of_post_thymectomy_autoimmunity__Role_of_syngeneic_MLR_reactive_T_cells_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=7759894 DB - PRIME DP - Unbound Medicine ER -