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Blood, 1 July 2006, Vol. 108, No. 1, pp. 203-208.
Prepublished online as a Blood First Edition Paper on February 14, 2006; DOI 10.1182/blood-2005-11-4330.


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IMMUNOBIOLOGY

Allogeneic T cells induce rapid CD34+ cell differentiation into CD11c+CD86+ cells with direct and indirect antigen-presenting function

Javaneh Abbasian, Dolores Mahmud, Nadim Mahmud, Sandeep Chunduri, Hiroto Araki, Pavan Reddy, Ronald Hoffman, Mario Arpinati, James L. M. Ferrara, and Damiano Rondelli

Section Hematology/Oncology, University of Illinois at Chicago; Departments of Pediatrics and Internal Medicine, University of Michigan Medical School, Ann Arbor; and Institute of Hematology and Medical Oncology "Seràgnoli," University of Bologna, Italy.

Dendritic cells (DCs) derive from CD34+ cells or monocytes and stimulate alloimmune responses in transplantation. We hypothesized that the interaction between CD34+ cells and allogeneic T cells would influence the function of hematopoietic stem cells (HSCs). Cord blood (CB) CD34+ cells proliferated briskly in response to allogeneic, but not autologous, T cells when mixed with irradiated T cells for 6 days in vitro. This proliferation was significantly inhibited by an anti-HLA class II monoclonal antibody (mAb), by an anti-TNF{alpha} mAb, or by CTLA4-Ig. Allogeneic T cells induced the differentiation of CD34+ progenitors into cells with the morphology of dendritic monocytic precursors and characterized by the expression of HLA-DR, CD86, CD40, CD14, and CD11c, due to an endogenous release of TNF{alpha}. Cotransplantation of CD34+ cells with allogeneic T cells into nonobese diabetic-severe combined immunodeficiency (NOD/SCID) mice resulted in a greater engraftment of myeloid CD1c+ dendritic cells compared with cotransplantation with autologous T cells. In vitro, CD34+ cell-derived antigen-presenting cells (APCs) were functionally capable of both direct and indirect presentation of alloantigens. Based on these findings, we hypothesize that in HSC transplantation the initial cross talk between allogeneic T cells and CD34+ cells may result in the increased generation of APCs that can present host alloantigens and possibly contribute to the development of graft-versus-host disease. (Blood. 2006;108:203-208)


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