Although this approach appears to have beneficial outcomes for many patients, some patients display relapse and disease progression ( 3– 6), suggesting room for improvement. The approach is based on the isolation and subsequent transfer of a patient’s stem cells following a preconditioning regimen designed to clear existing pathogenic clones. The challenge of treating autoimmune disease has initiated a range of new and novel approaches such as autologous hematopoietic stem cell transplantation (HSCT), which is currently being trialled in a range of disorders including multiple sclerosis (MS) ( 1– 3). This finding adds a further dimension to our understanding of the mechanisms of tolerance that are associated with this gene therapy approach to treating autoimmunity and may have important implications for Ab-mediated autoimmune disorders. In these animals, the development of MOG-specific B cells was abrogated, resulting in a lack of MOG-specific B cells in all B cell compartments examined. Using BM from IgH MOG mice that develop MOG-specific B cell receptors, we generated mixed chimeras together with BM-encoding MOG. However, the consequence of this strategy on B cell tolerance is not known.

We have previously shown in the mouse model of experimental autoimmune encephalomyelitis that transfer of bone marrow (BM) transduced with retrovirus encoding myelin oligodendrocyte glycoprotein (MOG) promotes disease resistance and CD4 + T cell deletion within the thymus. However, the capacity to genetically manipulate the immune system provides a powerful avenue to supplement this natural tolerance in an Ag-specific manner. The various mechanisms that have been described for immune tolerance govern our ability to control self-reactivity and minimize autoimmunity.

Mog meaning medical