Although TRI MP dosing used in this study was based on a pilot using daily injections of un-encapsulated drugs and a lower TRI dose provided limited arthritis protection (S2 Fig), it is possible that further optimization of dose and delivery kinetics to use a rapamycin dose in between that of high and low tested doses and/or lowering the rapamycin dose while increasing doses of TGF-β and IL-2 yields a formulation capable of preventing CIA development without causing systemic immunosuppression. This evidence concerns the gene TGFB1 and arthritic joint disease.