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Translational and Clinical Research |
1 Division of Stem Cell Transplantation, Department of Hematology/Oncology, St Jude Children's Research Hospital, Memphis, Tennessee
2 Integrated Research Center, St. Jude Children's Research Hospital, Memphis, Tennessee
3 Department of Pediatrics, University of Tübingen, Tübingen, Germany
* To whom correspondence should be addressed. E-mail: raymond.barfield{at}stjude.org.
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Abstract |
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Objective: To compare the patterns of T-cell differentiation from CD34+ human stem cells selected with different classes of antibody targeting the CD34 molecule.
Methods: We compared sjTREC production in thymocytes selected with different classes of anti-CD34 antibody. Based upon these results, we studied immune reconstitution in 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.
Results: Thymocytes selected with the 8G12 class III antibody have higher TREC production than those selected with the QBEnd class II antibody. Of mice transplanted with cells selected using the 8G12 antibody 50% had sj TREC production, compared with 14% of mice transplanted with cells selected using the clinically common antibody QBEnd.
Implications: 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.
Key Words. Immune reconstitution, hematopoietic stem cell transplantation, CD34 selection, CD34 progenitors, engraftment, Tcell, thymus, thymopoiesis
This article has been cited by other articles:
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  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]
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 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]
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