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TRANSLATIONAL AND CLINICAL RESEARCH

Selection of Stem Cells by Using Antibodies That Target Different CD34 Epitopes Yields Different Patterns of T-Cell Differentiation

^aDivision of Stem Cell Transplantation, Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA;
^bIntegrated Research Center, St. Jude Children's Research Hospital, Memphis, Tennessee, USA;
^cDepartment of Pediatrics, University of Tübingen, Tübingen, Germany

Key Words. Immune reconstitution • Hematopoietic stem cell transplantation • CD34 selection • CD34 progenitors • EngraftmentT cell • Thymus • Thymopoiesis

Correspondence: Raymond Barfield, M.D., Ph.D., Division of Stem Cell Transplantation, Department of Hematology/Oncology, St. Jude Children's Research Hospital, 332N Lauderdale Street, Memphis, Tennessee 38105-2794, USA. Telephone: 901-495-4720; Fax: 901-521-9005; e-mail: raymond.barfield{at}stjude.org

Received May 25, 2006; accepted for publication September 27, 2006.
First published online in STEM CELLS EXPRESS   October 5, 2006.



The objective of this study was to compare the patterns of T-cell differentiation from CD34⁺ human stem cells selected with different classes of antibody targeting the CD34 molecule. We compared signal-joint T-cell receptor excision circle (sjTREC) production in thymocytes selected with different classes of anti-CD34 antibody. Based on these results, we studied immune reconstitution in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice using human stem cells selected with the same antibodies that yielded variation in the thymocytes. Human CD34⁺ stem cells were immunomagnetically selected using the class II QBEnd antibody (prevalent in clinical graft engineering) and the class III 8G12 antibody (common in diagnostic tests). Engraftment and T-cell reconstitution were examined after transplantation. Thymocytes selected with the 8G12 class III antibody have a higher TREC production than those selected with the QBEnd class II antibody. Of mice transplanted with cells selected using the 8G12 antibody, 50% had sjTREC production, compared with 14% of mice transplanted with cells selected using the clinically common antibody QBEnd. 8G12 thymic progenitors are characterized by higher quality in thymic distribution and higher activity in T-cell differentiation. Using class III antibody targeting the CD34 molecule resulted in increased T-cell reconstitution in the NOD/SCID mouse. Use of a single antibody epitope targeting the CD34 molecule may lead to loss of cells that might provide richer T-cell reconstitution. Use of different or multiple epitopes, targeting of alternate stem cell markers, or use of cell-depletion strategies might prevent this loss.

This article has been cited by other articles:

				S. Hou, B. Li, L. Wang, W. Qian, D. Zhang, X. Hong, H. Wang, and Y. Guo Humanization of an Anti-CD34 Monoclonal Antibody by Complementarity-determining Region Grafting Based on Computer-assisted Molecular Modelling J. Biochem., July 1, 2008; 144(1): 115 - 120. [Abstract] [Full Text] [PDF]

				D. R. Sutherland and M. Keeney Re: Selection of Stem Cells by Using Antibodies That Target Different CD34 Epitopes Yields Different Patterns of T-Cell Differentiation Stem Cells, September 1, 2007; 25(9): 2385 - 2386. [Full Text] [PDF]