Short Course Immune Induction Therapy or SCIIT, is a therapeutic strategy employing rapid, specific, short term-modulation of the immune system using a therapeutic agent to induce T-cell non-responsiveness, also known as operational tolerance. As an alternative strategy to immunosuppression and antigen-specific tolerance inducing therapies, the primary goal of SCIIT is to re-establish or induce peripheral immune tolerance in the context of autoimmune disease and transplant rejection through the use of biological agents (compare also tolerogenic therapy). In recent years, SCIIT has received increasing attention in clinical and research settings as an alternative to immunosuppressive drugs currently used in the clinic, drugs which put the patients at risk of developing infection, cancer, and cardiovascular disease. Induction of immunological tolerance Immune tolerance can be defined as the ability of the immune system to distinguish between self and non-self, or harmless and harmful. T-cells are able to distinguish between self and non-self largely through their T-cell receptor, or TCR. Immune tolerance is maintained by central and peripheral tolerance. During central tolerance, T-cells are selected in the thymus and allowed to enter the periphery based on the ability of the T-cell to recognize self-peptides (via its TCR) being presented in the context of self-MHC. If the TCR binds the peptide-MHC complex with high affinity, the T cell is deleted from the host. In a healthy individual, this process eliminates the majority of T-cells that are self-reactive, although a few T-cells will escape thymic deletion. However, these potentially self-reactive cells in the periphery are held in check by a number of regulatory mechanisms such as active suppression by regulatory T cells(Tregs), clonal anergy, deletion, and ignorance. While autoimmunity is thought to result from the breakdown of central and peripheral tolerance, undesirable immune responses such as transplant organ rejection occur when the immune system is working properly and recognizes the transplanted organ as being non-self, leading to rejection of the transplanted tissue. In this context, manipulating the immune system to recognize the transplanted organ as self for the induction of immunological tolerance would be beneficial for the establishment of transplant tolerance. As autoimmunity and organ transplant rejection are inextricably linked to T-cell activation and differentiation, it is apposite that T-cells are the primary target of modern tolerance induction strategies. Current strategies for the treatment of T-cell mediated pathologies employ long-term, broad immunosuppressive drugs, which are moderately effective in limiting T-cell responses but carry unfavorable side effects,