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
- Stanford Univ. School of Medicine, CA (United States) Scripps Research Institute, La Jolla, CA (United States) PRESTO, JRDC, Institute of Phical and Chemical Research, Tsukuba, Ibaraki (Japan)
- Univ. of California, San Diego, LA Jolla, CA (United States)
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[sup +] T cells mediated the autoimmune prevention but CD8[sup +] T cells did not. CD4[sup +] T cells also appeared to mediate the TLI-induced autoimmune disease because CD4[sup +] 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. 62 refs., 9 figs., 2 tabs.
- OSTI ID:
- 6900782
- Journal Information:
- Journal of Applied Physiology (1985); (United States), Journal Name: Journal of Applied Physiology (1985); (United States) Vol. 73:5; ISSN JAPHEV; ISSN 8750-7587
- Country of Publication:
- United States
- Language:
- English
Similar Records
Two types of T helper cells in mice: Differences in cellular immune functions and cytokine secretion - selective reduction of one type after total lymphoid irradiation
Immune potentiation after fractionated exposure to very low doses of ionizing radiation and/or caloric restriction in autoimmune-prone and normal C57Bl/6 mice
Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOLOGICAL RADIATION EFFECTS
BLOOD
BLOOD CELLS
BODY FLUIDS
CONNECTIVE TISSUE CELLS
DISEASES
ETIOLOGY
IMMUNE SYSTEM DISEASES
LEUKOCYTES
LYMPHOCYTES
MATERIALS
RADIATION EFFECTS
SOMATIC CELLS