Comparative immunobiology of thymic DC mRNA in autoimmune-prone mice

New Zealand Black (NZB) mice have multiple defects in both innate and acquired immunity. A fundamental defect, described more than 25 years ago, is premature thymic involution. Subsequent studies have disclosed multiple defects in thymic epithelial cells, and it has been proposed that thymic dendritic cells (DCs) play an important role not only in thymic involution but also in the appearance of immunopathology. However, the number of available thymic DCs makes this population extremely difficult to study. We have taken advantage of our ability to isolate pure populations of thymic DCs and have examined several key mRNA levels of enzymes involved in signal transduction. Our data on NZB mice was compared to that of NZB x NZW F1 (B/WF1), BXSB-Yaa, MRL/lpr, NOD and control mice. Importantly, we demonstrate herein that a common feature in autoimmune-prone mice is an increase of thymic DC c-met mRNA. Indeed, the increase in c-met mRNA levels appeared specific to the thymus and was not noted in the spleen. Additionally, we demonstrate that E-cadherin, a downstream molecule of c-met, is also reduced. Finally, we note that the levels of HGF mRNA are normal in the autoimmune strains examined herein, confirming that the abnormality of c-met mRNA is not due to primary defects in thymic stromal cells. We submit that these results highlight the possibility of a selective defect in thymic DCs which will be a pivotal step in loss of tolerance, and suggest that future studies focus on adoptive cell transfer involving this population.