Autoreactive T-lymphocytes are implicated in the pathogenesis of bone marrow failure in patients with systemic lupus...

There is an increasing evidence that the trafficking and homing of autoreactive lymphocytes in the bone marrow (BM) of patients with systemic lupus erythematosus (SLE) may affect the haemopoiesis supporting capacity of BM stroma and may also damage haemopoiesis even at the level of the haemopoietic stem cell not only via direct immune destruction but also by an indirect effect due to the release of pro-inflammatory cytokines rendering stem cells sensitive to Fas-induced apoptosis. We have shown that the low BM CD34+ cell number in SLE is due to--at least in part--Fas up-regulation on these cells and subsequent apoptotic cell death induced by interferon-gamma- and Fas ligand- producing T-cells in the BM microenvironment. In accordance to previous reports demonstrating that co-culture of T-cells from SLE patients with autologous or allogeneic BM mononuclear cells may inhibit their clonogenic potential while removal of T-cells from patient BM samples may improve the in vitro colony formation, we have shown that intensive immunoablation followed by autologous stem cell rescue may restore the number and survival characteristics of BM CD34+ cells and the haemopoiesis supporting capacity of marrow stromal cells in these patients. The consideration of the complex interactions between autoreactive lymphocytes and haemopoietic progenitor cells in the BM may elucidate further the pathogenetic mechanisms underlying cytopenias in SLE and may provide an explanation for the difficulties in the stem cell collection procedure seen in SLE patients undergoing autologous stem cell transplantation.