Host T Cells Affect Donor T Cell Engraftment and Graft-versus-Host Disease after Reduced-Intensity Hematopoietic Stem Cell Transplantation

Abstract 

Mixed chimerism in the T cell compartment (MC_T) after reduced-intensity stem cell transplantation (RIST) may influence immune repopulation with alloreactive donor T cells. We examined effects of host T cell numbers on donor T cell engraftment and recovery and on acute graft-versus-host disease (aGVHD) in a relatively homogeneous patient population with respect to residual host T cells through quantified immune depletion prior to RIST and to donor T cells by setting the allograft T cell dose of 1 × 10⁵ CD3⁺ cells/kg. In this setting, 2 patterns of early donor T cell engraftment could be distinguished by day +42: (1) early and complete donor chimerism in the T cell compartment (FDC_T) and (2) persistent MC_T. FDC_T was associated with lower residual host CD8⁺ T cell counts prior to transplant and aGVHD. With persistent MC_T, subsequent development of aGVHD could be predicted by the direction of change in T cell donor chimerism after donor lymphocyte infusion, and no aGVHD occurred until FDC_T was established. MC_T did not affect recovery of donor T cell counts. These observations suggest that the relative number and alloreactivity of donor and host T cells are more important than the absolute allograft T cell dose in determining donor engraftment and aGVHD after RIST.

Key Words: Reduced-intensity stem cell transplantation, Graft-versus-host disease, T cells