Tags

Type your tag names separated by a space and hit enter

Ionizing radiation and autoimmunity. Induction of autoimmune disease in mice by high dose fractionated total lymphoid irradiation and its prevention by inoculating normal T cells.
J Immunol 1994; 152(5):2586-95JI

Abstract

Ionizing radiation can functionally alter the immune system and break self-tolerance. High dose (42.5 Gy), fractionated (2.5 Gy 17 times) total lymphoid irradiation (TLI) on mice caused various organ-specific autoimmune diseases, such as gastritis, thyroiditis, and orchitis, depending on the radiation dosages, the extent of lymphoid irradiation, and the genetic background of the mouse strains. Radiation-induced tissue damage is not the primary cause of the autoimmune disease because irradiation of the target organs alone failed to elicit the autoimmunity and shielding of the organs from irradiation was unable to prevent it. In contrast, irradiation of both the thymus and the peripheral lymphoid organs/tissues was required for efficient induction of autoimmune disease by TLI. TLI eliminated the majority of mature thymocytes and the peripheral T cells for 1 mo, and inoculation of spleen cell, thymocyte, or bone marrow cell suspensions (prepared from syngeneic nonirradiated mice) within 2 wk after TLI effectively prevented the autoimmune development. Depletion of T cells from the inocula abrogated the preventive activity. CD4+ T cells mediated the autoimmune prevention but CD8+ T cells did not. CD4+ T cells also appeared to mediate the TLI-induced autoimmune disease because CD4+ T cells from disease-bearing TLI mice adoptively transferred the autoimmune disease to syngeneic naive mice. Taken together, these results indicate that high dose, fractionated ionizing radiation on the lymphoid organs/tissues can cause autoimmune disease by affecting the T cell immune system, rather than the target self-Ags, presumably by altering T cell-dependent control of self-reactive T cells.

Authors+Show Affiliations

Department of Medicine, Stanford University School of Medicine, CA 94305.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

8133066

Citation

Sakaguchi, N, et al. "Ionizing Radiation and Autoimmunity. Induction of Autoimmune Disease in Mice By High Dose Fractionated Total Lymphoid Irradiation and Its Prevention By Inoculating Normal T Cells." Journal of Immunology (Baltimore, Md. : 1950), vol. 152, no. 5, 1994, pp. 2586-95.
Sakaguchi N, Miyai K, Sakaguchi S. Ionizing radiation and autoimmunity. Induction of autoimmune disease in mice by high dose fractionated total lymphoid irradiation and its prevention by inoculating normal T cells. J Immunol. 1994;152(5):2586-95.
Sakaguchi, N., Miyai, K., & Sakaguchi, S. (1994). Ionizing radiation and autoimmunity. Induction of autoimmune disease in mice by high dose fractionated total lymphoid irradiation and its prevention by inoculating normal T cells. Journal of Immunology (Baltimore, Md. : 1950), 152(5), pp. 2586-95.
Sakaguchi N, Miyai K, Sakaguchi S. Ionizing Radiation and Autoimmunity. Induction of Autoimmune Disease in Mice By High Dose Fractionated Total Lymphoid Irradiation and Its Prevention By Inoculating Normal T Cells. J Immunol. 1994 Mar 1;152(5):2586-95. PubMed PMID: 8133066.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ionizing radiation and autoimmunity. Induction of autoimmune disease in mice by high dose fractionated total lymphoid irradiation and its prevention by inoculating normal T cells. AU - Sakaguchi,N, AU - Miyai,K, AU - Sakaguchi,S, PY - 1994/3/1/pubmed PY - 1994/3/1/medline PY - 1994/3/1/entrez SP - 2586 EP - 95 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 152 IS - 5 N2 - Ionizing radiation can functionally alter the immune system and break self-tolerance. High dose (42.5 Gy), fractionated (2.5 Gy 17 times) total lymphoid irradiation (TLI) on mice caused various organ-specific autoimmune diseases, such as gastritis, thyroiditis, and orchitis, depending on the radiation dosages, the extent of lymphoid irradiation, and the genetic background of the mouse strains. Radiation-induced tissue damage is not the primary cause of the autoimmune disease because irradiation of the target organs alone failed to elicit the autoimmunity and shielding of the organs from irradiation was unable to prevent it. In contrast, irradiation of both the thymus and the peripheral lymphoid organs/tissues was required for efficient induction of autoimmune disease by TLI. TLI eliminated the majority of mature thymocytes and the peripheral T cells for 1 mo, and inoculation of spleen cell, thymocyte, or bone marrow cell suspensions (prepared from syngeneic nonirradiated mice) within 2 wk after TLI effectively prevented the autoimmune development. Depletion of T cells from the inocula abrogated the preventive activity. CD4+ T cells mediated the autoimmune prevention but CD8+ T cells did not. CD4+ T cells also appeared to mediate the TLI-induced autoimmune disease because CD4+ T cells from disease-bearing TLI mice adoptively transferred the autoimmune disease to syngeneic naive mice. Taken together, these results indicate that high dose, fractionated ionizing radiation on the lymphoid organs/tissues can cause autoimmune disease by affecting the T cell immune system, rather than the target self-Ags, presumably by altering T cell-dependent control of self-reactive T cells. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/8133066/Ionizing_radiation_and_autoimmunity__Induction_of_autoimmune_disease_in_mice_by_high_dose_fractionated_total_lymphoid_irradiation_and_its_prevention_by_inoculating_normal_T_cells_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=8133066 DB - PRIME DP - Unbound Medicine ER -