Long-term Consequences of²³⁹PuO₂Exposure in Dogs: Persistent T Lymphocyte Dysfunction

Abstract

Young Beagle dogs were exposed by inhalation to aerosols of 239PuO2 and observed for their lifespans as part of a large, ongoing study of the biological effects of inhaled radionuclides. The purpose of our study was to compare certain immune responses of the 239PuO2-exposed dogs at middle age (7-10 years old) and old age (12-14 years old), with those of unexposed, age-matched or young (3-4 years old) animals. Some of the aged, exposed dogs had developed lung tumours. Lymphocyte proliferative responses to phytohaemagglutinin (PHA) were lower in aged control dogs than in either young or middle-aged control dogs. Both aged and middle-aged, radiation-exposed dogs had decreased responses to PHA when compared to age-matched controls. Responses to concanavalin A (Con A) were not affected by age in control dogs, but tended to decrease in the oldest group of radiation-exposed dogs. Responses to both PHA and Con A were severely depressed in tumour-bearing dogs. The cytolytic activity of natural killer cells was not affected by age, radiation exposure, or tumour presence. We concluded that inhalation of 239PuO2 by young Beagle dogs resulted in an earlier-than-normal decrease in the ability of T cells to respond to mitogenic stimulation. In other words the depressed responses to PHA that were observed might represent radiation-induced, accelerated ageing of the T cell response.

Establishment of a microplate assay for flow cytometric assessment and it is use for the evaluation of age-related phenotypic changes in canine whole blood leukocytes

“…Percentages of T-and B-lymphocyte have been reported in different studies using PBMC phenotyping. In agreement with our findings, there is a major consensus of increased percentages of T and decreased percentage of B-cells in middle-aged dogs in comparison to young ones (Davila et al, 1992;Greeley et al, 1996;Faldyna et al, 2001;Toman et al, 2002). Significant age-related changes in percentage of CD4 + and CD8 + T-cell subsets have not been documented on the present study.…”

Effects of Age and Dietary β‐Carotene on Immunological Variables in Dogs

“…Studies with humans, rodents, and dogs have reported age-associated reductions in lymphoproliferative responses to various mitogens. 18,31,43 In the present study, interpretation of data for old dogs revealed depressed proliferative responses to the 3 mitogens that were used (Con A, PHA, and PWM) as well as the nonspecific DTH response to PHA when compared with young dogs and revealed a modest benefit of moderate or high ␤-carotene supplementation (Fig 4).…”

Animal Models for Medical Countermeasures to Radiation Exposure

“…Detailed investigations of the effects of 239 Pu inhalation found peripheral lymphopenia (30) and persistent T-cell dysfunction, although pulmonary immune responses to antigen seemed little affected (31), perhaps indicating the difficulty in extrapolating from systemic to local immune parameters. Long-term decreases in lymphocyte levels in dogs after external TBI also have been documented (32).…”