Magnetic Resonance Imaging of Radiation-Induced Thymic Atrophy as a Model for Pathologic Changes in Acute Feline Immunodeficiency Virus Infection

Abstract

The thymus is a primary lymphoid organ responsible for the production of a diverse repertoire of immunocompetent and self-tolerant T lymphocytes (T cells), vital for proper immune function. T lymphocyte differentiation, maturation, and proliferation occur as developing cells traffic through the thymic cortex and medulla in response to a multitude of cytokines and secreted factors. The thymus undergoes physiologic involution due to aging, but also undergoes pathologic atrophy due to a variety of causes, including infectious diseases, endocrine disturbances, nutritional disorders, chemotherapeutics, or radiation injury. In particular, feline immunodeficiency virus (FIV) infection causes significant alteration and destruction of the thymus, leading to compromise and dysfunction of the host immune system and rendering individuals susceptible to opportunistic infections, primarily through a reduction in CD4+ T lymphocytes and an impairment of cell-mediated immunity. As the cat is smallest known natural model for lentiviral infection, and FIV is a significant, worldwide disease in domestic and wild cats, research involving the pathogenesis, consequences, treatment and prevention of FIV infection are of great importance. However, thymic changes often vary due to a multitude of host, pathogen, and environmental factors. A method to produce a controlled, reproducible, and highly consistent in vivo model of thymic atrophy was developed in this study, through the application of a single, directed dose of x-irradiation to four, 8 to12-week-old kittens. Identification, quantification, and analysis of thymic changes in irradiated and normal, age-matched subjects, were conducted using a magnetic resonance imaging protocol specifically developed to provide maximum visualization of the juvenile feline thymus. Following irradiation, marked thymic atrophy was confirmed morphometrically and histologically, and was similar to changes reported during acute FIV infection. By 7 to 14 days post-irradiation, there was a gradual rebound in thymic size, which in some instances approached pre-irradiation values. These findings demonstrate the feasibility and advantages of using a non-invasive, in vivo imaging technique in order to measure and evaluate changes in thymic volume, as a model for pathologic changes noted in acute FIV infection.