Abstract 1486: CD127 is Required for Macrophage and Regulatory T Cell Function and Has a Protective Role in Atherosclerosis
CD127 is the receptor for interleukin 7 (IL-7) and is expressed on immature B cells, activated T cells, macrophages and vascular endothelial cells. IL-7 induces Th1 cell activation via CD127, and is essential for the survival of regulatory T cells. Furthermore, premature B cells need IL-7 to proliferate into mature B cells. In LDLr−/− mice CD127 mRNA was upregulated 5-fold (p<0.001) in the aortic arch after 9 weeks of Western type diet, indicating a correlation between expression of CD127 and atherosclerotic lesion formation. In order to elucidate the function of CD127 in the process of atherosclerosis we constructed an anti-CD127 DNA vaccine by cloning murine CD127 into pcDNA3.1. Vaccination was performed by repeated oral administration of attenuated Salmonella typhimurium transformed with pcDNA3.1-CD127. The vaccination resulted in a CD8 mediated cytotoxic response to cells expressing high levels of CD127. Vaccination of LDLr−/− mice against CD127 aggravated collar induced lesion formation by 267% (p=0.004) with no effects on serum cholesterol levels. Lesions from vaccinated mice showed reduced plaque cellularity (2.8*10−3 vs. 4.1*10−3 nuclei/μm2, p=0.03) and increased apoptotic area (5.2 *103 vs. 1.2*103 TUNEL area/intima, p=0.05) compared to control vaccinated animals. IgG1, IgG2a and IgM antibody titers against oxidized LDL were not altered after vaccination, indicating a normal functional B cell population. However, CD127 expression on B cells in the spleen was significantly decreased by 33% by vaccination (p<0.01). Macrophage numbers in spleens from vaccinated mice were reduced by 37% (p=0.02), CD4 and CD8 T cell percentages in spleen, lymph nodes and blood were not altered. Strikingly, the regulatory T cell population (CD4CD25) in draining lymph nodes from the aortic arch was significantly decreased by 30% (p=0.02). We conclude from these results that CD127 is an essential factor in the functionality or survival of regulatory T cells and macrophages, which may contribute to its protective role in the process of atherosclerotic lesion formation.