Chronic IFN-gamma expression alters the migration pattern of peripheral T cells (160.7)

Abstract

Abstract We report here on preliminary data from an IFN-gamma(IFN-γ)ARE-deleted Balb/c mouse model developed in our laboratory.This mouse has a 162 nt deletion in the 3’untranslated region of the IFN-γ mRNA to eliminate an AU-rich sequence. The deletion has a positive impact on IFN-γ mRNA accumulation by dramatically increasing its half-life. In the absence of stimulatory factors,these mice express low level of IFN-γ constitutively. IFN-γ ARE-deletion results in a severe phenotype on Balb/c mice. The knockout (KO) and heterozygous (Het) mice are smaller in size than the littermate controls, have a rough coat and a low survival rate after weaning. Additionally, these mice have an enlarged thymus with an increased percentage of mature naïve T cells. The mature thymocytes from Het animals are able to leave the thymus and enter peripheral lymphoid tissues. However, the results from chimera experiments indicate that IFN-γ may impact the thymic environment, thus resulting in abnormal T cell development. In addition, we found the migration pattern of peripheral T cells from Het mice differs from that observed with cells from control animals, further suggesting an abnormality in the Het T cell physiology. Current experiments focus on analyzing changes in the thymic environment and T cell development in newborn mice. In addition, we are analyzing chemokine receptor expression to determine if changes in these receptors may be a mitigating factor in the T cell migration patterns.