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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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Submitted November 2, 2005
Accepted February 6, 2006

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 Ferrara, and Damiano Rondelli*

Section of Hematology/Oncology, University of Illinois at Chicago, Chicago, Illinois, USA
Departments of Pediatrics and Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
Institute of Hematology and Medical Oncology Seragnoli, University of Bologna, Bologna, Italy

* Corresponding author; email: drond{at}uic.edu.

Dendritic cells (DC) 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 (HSC). 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, CD11c, due to an endogenous release of TNF{alpha}. Co-transplantation of CD34+ cells with allogeneic T-cells into NOD/SCID mice resulted in a greater engraftment of myeloid CD1c+ dendritic cells, compared to co-transplantation with autologous T-cells. In-vitro, CD34+ cells-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 crosstalk 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-vesus-host disease.


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