Cellular and Molecular Phenotypes of pConsensus Peptide (pCons) Induced CD8 and CD4 Regulatory T Cells in Lupus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with widespread inflammation, immune dysregulation, and is associated with the generation of destructive anti-DNA autoantibodies. We have shown previously the immune modulatory properties of pCons peptide in the induction of both CD4 and CD8 regulatory T cells which can in turn suppress development of the autoimmune disease in (NZB/NZW) F1 (BWF1) mice, an established model of lupus. In the present study, we add novel protein information and further demonstrate the molecular and cellular phenotypes of pCons-induced CD4 and CD8 T subsets. Flow cytometry analyses revealed that pCons induced CD8 T cells with the following cell surface molecules: CD25CD28 subsets (shown earlier), CD62L, CD122, PD1, CTLA4, CCR7 and 41BB. Quantitative real-time PCR (qRT-PCR) gene expression analyses revealed that pCons-induced CD8 T cells downregulated the following several genes: Regulator of G protein signaling (, programmed cell death Further, we confirmed the down regulation of these genes by Western blot analyses at the protein level. To our translational significance, we showed herein that pCons significantly increased the percentage of CD8FoxP3 T cells and further increased the mean fluorescence intensity (MFI) of FoxP3 when healthy peripheral blood mononuclear cells (PBMCs) are treated with pCons (10 μg/ml, for 24-48 hours). In addition, we found that pCons reduced apoptosis in CD4 and CD8 T cells and B220 B cells of BWF1 lupus mice. These data suggest that pCons stimulates cellular, immunological, and molecular changes in regulatory T cells which in turn protect against SLE autoimmunity.