Profound depletion of host conventional dendritic cells plasmacytoid dendritic cells and B cells does not prevent GVHD induction

摘要

The efficacy of alloSCT is limited by graft-versus-host disease (GVHD). Host hematopoietic antigen presenting cells (APCs) are important initiators of GVHD making them logical targets for GVHD prevention. Conventional dendritic cells (cDCs) are key APCs for T cell responses in other models of T cell immunity and they are sufficient for GVHD induction. However, we report here in two polyclonal GVHD models in which host hematopoietic APCs are essential, that GVHD was not decreased when recipient cDCs were inducibly or constitutively deleted. Additional profound depletion of plasmacytoid DCs and B cells, with or without partial depletion of CD11b⁺ cells, also did not ameliorate GVHD. These data indicate that, in contrast to pathogen models, there is a surprising redundancy as to which host cells can initiate GVHD. Alternatively, very low numbers of targeted APCs were sufficient. We hypothesize the difference in APC requirements in pathogen and GVHD models relates to the availability of target antigens. In anti-pathogen responses specialized APCs are uniquely equipped to acquire and present exogenous antigens whereas in GVHD all host cells directly present alloantigens. These studies make it unlikely that reagent-based host APC depletion will prevent GVHD in the clinic.