Potential for cytokine and product manipulation to improve the results of autologous stem cell transplantation for rheumatoid arthritis

The eradication of autoreactive T cells by high dose therapy and stein cell transplantation and the resultant alterations in the immunologic network, thymic reeducation, and peripheral tolerance provide treatment mechanisms f or autoimmune and inflammatory diseases. One outcome of autologous stein ce ll transplantation is a significant decrease in the CD4:CD8 ratio due to a loss in CD4+ cells and a depression in T cell function. Mechanistically, th e loss of T cell function is associated with an increased frequency of circ ulating monocytes, their expression of Fas ligand (FasL). and it high frequ ency of apoptotic CD4+ T cells. This suggests that activated Fas+ CD4+ lymp hocytes interact with FasL+ monocytes, resulting in apoptosis, preferential deletion of CD4+ T cells, an inversion in the CD4:CD8 ratio, and depressed T cell function. These observations suggest the potential for immune regul ation using stem cell manipulation or posttransplant cytokine administratio n its therapeutic strategies for autoimmune/inflammatory diseases.