Enhanced Histopathology of Lymphoid Tissues

Enhanced histopathology of the immune system is a tool that the pathologist can use to assist in the identification of immunomodulatory drugs and chemicals. This assessment is based on the assumption that compound induced-alterations (drug or chemical) may produce changes in cell production and cell death as well as cellular trafficking and recirculation, which will be histologically expressed as alterations in cellular density or compartment sizes in lymphoid organs (Vos, 1980; Vos and Dean, 1990; Schuurman et al., 1994; Basketter et al., 1995; Harleman 2000; Ruehl-Fehlert et al., 2005). Enhanced histopathology involves the subjective and semiquantitative histological evaluation of various lymphoid organs and their respective tissue compartments to identify specific cellular and architectural changes. Although this methodology cannot directly measure immune function, in conjunction with gross changes, organ weights, hematologic measurements, and clinical chemistry, it does have the potential to determine whether or not exposure to a specific compound may cause suppression or enhancement of the immune system (ICICIS, 1998; Schulte et al., 2002; Germolec et al., 2004). An inherent limitation of any histological evaluation is its static representation of a dynamic process, and this is especially true for lymphoid tissues. As with all screening tests, evaluation of, and comparison with, control tissues is crucial in order to establish the range of normal tissue changes for a particular group of animals (Kuper et al., 2000). Laboratory animals include species other than rat and mouse; therefore, recognition of species differences in the structure and function of the immune system should be noted, as well as identification of which differences are biologically relevant for the endpoint being considered (Haley, 2003). Consideration should also be given to the overall health, nutritional status, antigen load, age, spontaneous lesions, steroid hormone status, and apparent stress for each strain and group of animals (Odio et al., 1987; Levin et al., 1993; Gopinath 1996). It is important to note that the distinction between a direct immunotoxic effect of a chemical as compared to secondary stress-related tissue changes can be challenging. Stress-induced lymphoid lesions and lesions caused by direct effects of chemical treatment can be identical. Interpretation of stress-related changes should be based on the combination of clinical signs and other study data, such as decreased body weight gain and decreased activity, as well as complete blood cell count (CBC) results, increased adrenal gland weights, decreased thymus weight, decreased thymic cortical cellularity with associated lymphocyte apoptosis, and changes in spleen and lymph node cellularity.