The Effects Of Farnesyltransferase Inhibitor Abt-100 On Murine Helper T-Cell Differentiation And Cytokine Secretion

Farnesyltransferase Inhibitors (FTIs) are a class of drugs known to prevent the farnesylation and subsequent membrane attachment of a number of intracellular proteins. In various studies, the administration of FTIs has been found to play a role in the activation and development of T-cells in the immune system. FTIs have also been found to act as immunomodulators in delaying MHC-II mismatched skin allografts in mice. This study focuses on the effect of the FTI, ABT-100, on the differentiation and cytokine secretion of Th1 and Th2 helper T-cells in BALB/C mice to better understand which immune responses are targeted by FTIs. Splenocytes were isolated from BALB/C mice, skewed towards either a Th1 or a Th2 phenotype with the addition of cytokines, and treated with various concentrations of ABT-100. Splenocytes were also isolated and immediately cultured in the presence of ABT-100 to observe differentiation trends of helper T-cells. Cytokine production was measured using intracytoplasmic flow cytometry analysis. I found that ABT-100 treatment does not block Th1 or Th2 cell differentiation. Instead, ABT-100 treatment appears to affect cytokine production from effector T-cells. I found that ABT-100 causes a decrease in IFN-¿ production in mature Th1 cells yet does not affect IL-4 production in mature Th2 cells. This decrease in cytokine production as a result of ABT-100 treatments provides a potential mechanism for how ABT-100 works to delay MHC-II mismatched allograft rejection.

A Measurement Model of Cortisol Reactivity of Healthy Older Adults

Research on the physiological adaptation process has found that stress is associated with the rate of cortisol secretion, the main hormone that reflects stress. However, considerable variation among subjects has been reported. Using a sample of older adults (N=46), we tested the hypothesis that cortisol reactivity is composed of (1) a situation-related component representing hypothalamic influence on cortisol secretion observed on three different occasions, and (2) a stable component representing a general trait responsible for cortisol responses observed from occasion to occasion. LISREL VIII was used to test this hypothesis. Results indicated that a homogeneous reliability model was not supported by the data. A congeneric measurement model represented a better fit to the data. Results suggest that subjects have consistent patterns of response during separate experimental occasions. However, results do not suggest a consistent pattern of response over time. The main implication of these results is that salivary cortisol measures are sensitive to experimental stress situations. As such, this noninvasive method may be useful in examining adaptive responses to stress.