Splenocytes can replace chimeric cells and maintain allograft tolerance

Abstract

Background: The induction of donor-specific tolerance (DST) has recently attracted widespread attention as a new approach to facilitate engraftment without using immunosuppressants. One way in which to induce DST is to establish a chimeric state that allows donor-derived cells to exist within a recipient. This study aims to investigate whether splenocytes can be used to maintain chimerism and to prolong graft survival.

Methods: Mixed bone marrow (BM) was established in this chimeric model by lethally irradiating C3H mice on day 0, and transplanting BM from C3H and B6D2F1 mice into them. Skin grafts from C57BL/6 mice were transplanted on day 30. On day 60, splenocytes from C3H (group A), B6D2F1 (group B) and B6C3F1 (group C) mice were administered to the chimeric mice. The class I major histocompatibility complex (MHC) type, the percentage of chimeric cells in the peripheral blood, and the survival of skin grafts were assessed.

Results: After splenocyte infusion, BM-derived chimeric cells were eliminated from the periphery in group A (86.2+/-5.9% to 0.04+/-0.03%, P=0.0008), B6D2F1-derived cells increased in quantity and established an allochimera in group B (83.7+/-7.2% to 99.6+/-0.2%, P=0.021), and in group C the B6C3F1-derived cells significantly increased to a level of 77.8% at 180 days after infusion (P=0.014), thereby maintaining the new chimerism. Skin grafts in groups B and C survived for at least 200 days (P=0.0003 and P=0.0001, respectively).

Conclusions: Chimerism arising from cells with a partial MHC match to the graft allows the maintenance of specific immunotolerance and graft survival.