Cord blood nucleated cells induce delayed T cell alloreactivity.
Cord blood (CB) mononuclear cells (MNCs) can be transplanted in HLA mismatched recipients with limited graft rejection or graft-versus-host disease (GVHD). Previous studies have shown that naive T cells and hyporesponsive dendritic cells are largely represented in CB. Data presented here demonstrate that CB MNCs are unable to stimulate allogeneic T cell proliferative or cytotoxic responses in standard in vitro assays. However, a suppressive effect of CB MNCs was ruled out because purified CD34(+) cells or CD14(+) monocytes stimulated T cell responses that were not inhibited by add-back of CB MNCs. The lack of antigen-presenting cell (APC) activity of CB MNCs in primary mixed lymphocyte culture (MLC) did not induce allogeneic T cell anergy. In fact, rechallenge of T cells with CB CD34(+) cells, or immature monocyte-derived dendritic cells (iMo-DCs) in secondary MLC induced potent T cell proliferative responses. A delayed APC activity of CB MNCs was observed after stimulation with irradiated allogeneic T cells for 6 days, likely because of the upregulation of CD86 and HLA-DR on CB cells. Cytotoxic lymphocytes (CTL) were generated after stimulation of blood T cells with CB MNCs for 4 weeks or CB-derived iMo-DCs for 1 week. Concomitant stimulation of T cells with CB iMo-DC obtained from 2 CB units resulted in the generation of CTLs specific for each CB, independently of the CB:CB cell ratio. These data suggest that the APC activity of CB cells possibly increases posttransplant, and may contribute to delayed graft rejection and/or acute and chronic GVHD.
Chunduri
Sandeep
S
Section Hematology/Oncology, University of Illinois at Chicago, Chicago, Illinois 60612-7323, USA.
Mahmud
Dolores
D
Abbasian
Javaneh
J
Arpinati
Mario
M
Rondelli
Damiano
D
D017951:Antigen Presentation; D049109:Cell Proliferation; D005312:Fetal Blood / Q000166:cytology* / Q000276:immunology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007519:Isoantigens; D008213:Lymphocyte Activation / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology
D007519:Isoantigens