Tolerance associated with cord blood transplantation may depend on the state of host dendritic cells.
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-gamma (IFN-gamma) 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-gamma and down-regulated IL-10 production levels from CB CD4(+) T cells to that from adult blood CD4(+) T cells. The sustained low IFN-gamma 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.
Division of Respiratory Disorders, Children's Hospital, Chongqing University of Medical Sciences, Chongqing, China.
Enmei
E
Liu
Helen K W
HK
Law
Yu-Lung
YL
Lau
D000328:Adult; D000375:Aging / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D023201:CD40 Ligand / Q000097:blood; D018920:Coculture Techniques; D036101:Cord Blood Stem Cell Transplantation; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000097:blood; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000097:blood; D023001:Transplantation Tolerance / Q000276:immunology*; D014373:Tuberculin / Q000276:immunology
D008070:Lipopolysaccharides; D015375:Receptors, Interleukin-2; D014373:Tuberculin; D016753:Interleukin-10; D023201:CD40 Ligand; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens