The Yin and Yang of adaptive immunity in allogeneic hematopoietic cell transplantation: Donor antigen-presenting cells can either augment or inhibit donor T cell alloreactivity

The immunoregulatory activity of different donor bone marrow (BM) cell subsets has not yet been fully addressed in allogeneic transplantation. We studied whether manipulation of donor antigen-presenting cells (APC) can affect posttransplant immunity using a mouse model of allogeneic bone marrow transplantation (BMT). CD11b is a marker present on mature monocytes, granulocytes, and a subset of dendritic cells (DC). In order to manipulate the content of APC, we enriched or depleted CD11b cells from BM grafts using immuno-magnetic cell sorting. The effect of CD11b depletion on graft-versus-host disease (GvHD) and graft-versus-leukemia (GvL) was studied in a MHC fully mismatched model of allogeneic BMT using C57BL/6 → B10.BR transplants and LBRM cells, a B10.BR T cell leukemia cell line. Transplantation with CD11b partially or fully depleted BM and low-dose donor splenocytes conferred 40% long-term leukemia- free survival with minimal GvHD when supralethal doses of LBRM were administered before transplant, or 75 days after BMT. Higher levels of serum gamma interferon and expansion of spleen-derived CD4 memory T cells were seen among recipients of CD11b-depleted BM compared to recipients of unmanipulated BM. Expansion of donor-spleen-derived T cells was inversely proportional to the content of CD11b cells in the BM graft. Thus, manipulating the content of APC subsets in donor BM by enriching or removing CD11b cells had a direct effect on post-transplant immunity and the balance between donor T cell activation (Yang) and donor T cell tolerance/anergy (Yin). © 2007 Springer Science+Business Media, LLC.