Tolerance associated with cord blood transplantation may depend on the state of host dentritic cells

Abstract

Allogeneic cord blood (CB) transplantation is associated with less severe graft-versus-host disease (GvHD), thought to be due to the immaturity of CB T cells, but how T cells interact with host and donor-derived dendritic cells (DCs) to initiate GvHD has not been elucidated. We therefore investigated the responses of CB and adult blood CD4 + T cells co-cultured with adult host DCs of different maturities. Primed by adult host DCs, CB and adult blood CD4 + T cells underwent similar changes in the expression of CD45RA/45RO, CD25, CD40L and CTLA-4. However, CB CD4 + T cells, when primed by either immature or Bacillus Calmette-Guerin mycobacteria-treated adult host DCs, produced lower interferon-γ (IFN-γ) and higher interleukin-10 (IL-10), which is a regulatory T cell-like cytokine profile, as compared with adult blood CD4 + T cells. In contrast, lipopolysaccharide (LPS)-treated adult host DCs significantly up-regulated IFN-γ and down-regulated IL-10 production levels from CB CD4 + T cells to that from adult blood CD4 + T cells. The sustained low IFN-γ and high IL-10 production from CB CD4 + T cells co-cultured with adult blood DCs might account for the less severe GvHD occurrence after CB transplantation, which could be reversed by LPS-treated adult blood DCs.