TY - JOUR T1 - Potential for cytokine and product manipulation to improve the results of autologous stem cell transplantation for rheumatoid arthritis. JF - The Journal of Rheumatology JO - J Rheumatol SP - 32 LP - 38 VL - 64 AU - J E Talmadge AU - R Singh AU - A Ageitos AU - S Buyukberber Y1 - 2001/10/01 UR - http://www.jrheum.org/content/64/32.abstract N2 - The eradication of autoreactive T cells by high dose therapy and stem cell transplantation and the resultant alterations in the immunologic network, thymic reeducation, and peripheral tolerance provide treatment mechanisms for autoimmune and inflammatory diseases. One outcome of autologous stem cell 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, the loss of T cell function is associated with an increased frequency of circulating monocytes, their expression of Fas ligand (FasL), and a high frequency of apoptotic CD4+ T cells. This suggests that activated Fas+ CD4+ lymphocytes 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 regulation using stem cell manipulation or posttransplant cytokine administration as therapeutic strategies for autoimmune/inflammatory diseases. ER -