Previously, we reported that
intravenous infusion of apoptotic leukocytes facilitated bone marrow (BM) engraftment across major histocompatibility barriers. This cell-based therapeutic approach is of great interest for stem cell
therapy across histocompatibility barriers. Autoimmunity associated with apoptotic cell administration may, however, limit the use of this approach. Indeed,
autoantigens are concentrated on the surface of apoptotic cells, and defective clearance of apoptotic bodies is associated with the occurrence of systemic
autoimmune disease. In consequence, we assessed the autoimmune responses raised against ubiquitous
double-stranded DNA (dsDNA) and
cardiolipin autoantigens following a single
intravenous infusion of apoptotic cells simultaneously to allogeneic BM administration. No difference was observed between levels of natural circulating
immunoglobulin M (
IgM) (anti-dsDNA and anti-
cardiolipin) autoantibodies found in mice receiving allogeneic BM alone and those found in mice receiving apoptotic cells also. Pathogenic
IgG autoantibody titers after apoptotic cell infusion were 9- to 200-fold lower than
autoantibody titers found in lupus-prone mice and not different from titers detected in BM grafted mice. Kinetic analysis of
autoantibodies after
transplantation did not demonstrate any immunization against tested
autoantigens after apoptotic cell infusion. Finally, neither
immune complex deposition nor specific lesions were observed in the renal glomeruli of mice infused with apoptotic cells 9 months post-BM
transplantation. Overall, these results show no specific toxicity of a single infusion of apoptotic cells administrated simultaneously to BM and may also shed light on factors influencing the immunogenic properties of apoptotic cells.