Immune potentiation after fractionated exposure to very low doses of ionizing radiation and/or caloric restriction in autoimmune-prone and normal C57Bl/6 mice.
Very low doses of ionizing radiation can enhance immune responsiveness and extend life span in normal mice. Total lymphoid irradiation at relatively high doses of radiation can retard autoimmune disease in genetically susceptible mice, but may impair immune function. In order to determine whether fractionated low dose exposure would enhance immune response and retard lymphadenopathy in autoimmune-prone mice, groups of C57B1/6 lpr/lpr mice were sham irradiated, exposed 5 days/week for 4 weeks to 0.04 Gy/day (0.8 Gy cumulative dose), or to 0.1 Gy/day (2.0 Gy cumulative dose). After the radiation protocol, the mice were evaluated for splenic T cell proliferative capacity, T cell subset distribution, and total spleen cell numbers. The independent and additive effect of caloric restriction was additionally assessed since this intervention has been shown to increase immune responsiveness and retard disease progression in autoimmune-prone mice. The congenic C57B1/6 +/+ immunologically normal strain was evaluated in parallel as congenic control. The results indicated that mitogen-stimulated proliferation was up-regulated in both strains of mice after exposure to 0.04 Gy/day. The proliferative capacity was additively enhanced when radiation at this dose level was combined with caloric restriction. Exposure to 0.1 Gy/day resulted in further augmentation of proliferative response in the lpr/lpr mice, but was depressive in the +/+ mice. Although the proportions of the various T cell subpopulations were altered in both strains after exposure to LDR, the specific subset alterations were different within each strain. Additional experiments were subsequently performed to assess whether the thymus is required for LDR-induced immune potentiation. Thymectomy completely abrogated the LDR effect in the +/+ mice, suggesting that thymic processing and/or trafficking is adaptively altered with LDR in this strain. In contrast, augmentation in proliferative activity after LDR in the lpr/lpr mice was maintained, although attenuated, in thymectomized mice. Taken together, these results indicate that fractionated exposure to LDR augments the proliferative response of spleen cells in both autoimmune-prone and immunologically normal mice; however, within each strain, the mechanisms appear to be different.
James
S J
SJ
Geriatric Research, Education and Clinical Center, VA Medical Center, West Los Angeles, California 90073.
Enger
S M
SM
Peterson
W J
WJ
Makinodan
T
T
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D002452:Cell Count / Q000528:radiation effects; D004195:Disease Models, Animal; D002149:Energy Intake / Q000276:immunology*; D007107:Immune System / Q000528:radiation effects*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010835:Phytohemagglutinins / Q000494:pharmacology; D011829:Radiation Dosage; D013154:Spleen / Q000166:cytology; D013934:Thymectomy; D013950:Thymus Gland / Q000166:cytology; D013997:Time Factors
D010835:Phytohemagglutinins