Background: Following allogeneic bone marrow transplantation there is rapid replacement of host antigen presenting cells with donor antigen presenting cells. This has important implications of the mechanisms of alloantigen presentation that results in graft-vs-host disease (GVHD). However, the kinetics of this process are not well understood.

Methods: Lethally irradiated BALB/c mice were the recipients of 10^7 B6 bone marrow and 10^6 B6 lymphocytes by intravenous injection. This model leads to lethal GVHD in 3 to 4 wks. On a weekly basis, bone marrow recipients were injected with 2×10^6 CFSE-labelled, purified CD4+ T cells from 4C T cell receptor transgenic mouse. The 4C mouse has CD4+ T cells with direct alloreactivity against the BALB/c MHC-class II molecule, I-Ad. Three days after injection, splenocytes and intrahepatic lymphocytes were purified and analyzed by FACS. Transferred 4C T cells were identified in host mice by as Ly5.1+, CD4+ cells. Lymphocytes obtained from host mice were analyzed by FACS for host vs. donor MHC expression at various time points after transplantation.

Results: Even at late time points, when host antigen presenting cells are undetectable by histology or FACS, 4C T cells proliferate robustly in BALB/c recipients of B6 bone marrow transplantation, even with the addition of lethal amount of allogeneic lymphocytes. FACS analysis of host lymphocytes demonstrates a substantial population with mixed host and donor MHC molecules.

Conclusions: These results demonstrate that direct CD4+ alloantigen recognition occurs at late time points following allo-BMT. Lymphocytes with donor and host mixed MHC expression, potentially obtained through the process of trogocytosis, may account for an unrecognized pool of host alloantigen that can lead to late onset acute GVHD.

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