ApoSalvianolic-acid-B lipoprotein A-I is the main protein of high-density lipoprotein and mediates efflux of cellular cholesterol from the peripheral tissues to the liver for excretion from the body in feces. This transport process, the so-called reverse cholesterol transfer pathway, involves a number of participating membrane proteins and plasma enzymes including ATP-binding casse e transporters A1 and G1, scavenger receptor BI, and lecithin cholesterol-acyl transferase enzyme, the la er being associated with maturation of HDL in plasma. In addition, HDL is involved in antiinflammatory and anti-oxidant processes that occur through nonRCT pathways. Several variants of apoA-I with altered functionality have been identified. The first naturally occurring variant of apoA-I described was the apoA-I Milano variant, which was identified in a family originating from the village of Limone sul Garda in northern Italy. The single mutation of this variant results in a substitution of Arg to Cys in the primary structure at residue 173. Described carriers of the Milano variant of apoA-I are heterozygotes and have very low plasma levels of apoA-I and HDL cholesterol as well as normal or moderately elevated plasma triglycerides. Despite this pro-arteriosclerotic lipoprotein profile, carriers of the apoAI-M variant display no increase in cardiovascular disease or events at the preclinical level. In fact, the RCT capacity of apoAI-M carriers is enhanced and the variant also exhibits anti-inflammatory and plaque stabilizing properties. The beneficial effect of infusion of recombinant apoAI-M has been shown by reduction of atherosclerotic lesions in experimental animal models. Clinical trials have also demonstrated a reduction of atheromas after repeated administration of apoAI-M/phospholipid complexes to patients with coronary disease. Clearly, the Milano variant provides positive effects on the cardiovascular system. However, the location of the R173C amino acid substitution is in a region of the apoA-I primary structure that is known to harbor several fibrillogenic variants, which lead to tissue specific plaque formation of the fibrillogenic protein and consequent organ failure. Considering the location of the amino acid substitution to this region and that the Milano variant is currently under investigation as an infusion therapy in cardiovascular disease, we wished to understand its susceptibility to aggregation. We have here examined the intrinsic propensity of the apoAI-M variant to aggregate into fibrils. T cell activation is determined by intrinsic cellular factors consisting of T cell receptor signaling and costimulatory Ergosterol signals. However, other extrinsic factors such as cytokines and products of cell death also affect T cell activation, differentiation, and survival by modulating cell intrinsic signals. T cell differentiation may be affected by activating pathways involving recruitment of lck and other signaling molecules. In addition, activation of innate immune receptors and signaling pathways can also modulate T cell differentiation. Previous studies showed that the receptor for glycation end products plays a role in activation and differentiation of T cells. Blockade of RAGE activation with soluble RAGE a enuated the adoptive transfer of diabetes in NOD mice and also reduced recurrent diabetes.