Consequences of exposure to ionizing radiation for effector T cell function in vivo.
The adoptive transfer of actuely primed and memory virus-immune CD8+ T cells causes enhanced meningitis in both cyclophosphamide (Cy) suppressed, and unsuppressed, recipients infected with lymphocytic choriomeningitis virus (LCMV). The severity of meningitis is assessed by counting cells in cerebrospinal fluid (CSF) obtained from the cisterna magna, which allows measurement of significant inflammatory process ranging from 3 to more than 300 times the background number of cells found in mice injected with virus alone. Exposure of the donor immune population to ionizing radiation prior to transfer has shown that activated T cells from mice primed 7 or 8 days previously with virus may still promote a low level of meningitis in unsuppressed recipients following as much as 800 rads, while this effect is lost totally in Cy-suppressed mice at 600 rads. Memory T cells are more susceptible and show no evidence of in vivo effector function in either recipient population subsequent to 400 rads, a dose level which also greatly reduces the efficacy of acutely-primed T cells. The results are interpreted as indicating that heavily irradiated cells that are already fully functional show evidence of primary localization to the CNS and a limited capacity to cause pathology. Secondary localization, and events that require further proliferation of the T cells in vivo, are greatly inhibited by irradiation.
Rouse
B T
BT
Department of Microbiology, University of Tennessee, Knoxville.
Hartley
D
D
Doherty
P C
PC
D000818:Animals; D002455:Cell Division / Q000528:radiation effects; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000528:radiation effects; D007116:Immunization, Passive; D007165:Immunosuppression Therapy; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011839:Radiation, Ionizing; D013601:T-Lymphocytes / Q000502:physiology* / Q000528:radiation effects
D003520:Cyclophosphamide