Selection of stem cells by using antibodies that target different CD34 epitopes yields different patterns of T-cell differentiation.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Otto, M; Chen, X; Martin, WJ; Leung, W; Knowles, J; Holladay, M; Houston, J; Handgretinger, R; Barfield, RC

Published Date

  • February 2007

Published In

Volume / Issue

  • 25 / 2

Start / End Page

  • 537 - 542

PubMed ID

  • 17023516

Pubmed Central ID

  • 17023516

International Standard Serial Number (ISSN)

  • 1066-5099

Digital Object Identifier (DOI)

  • 10.1634/stemcells.2006-0319

Language

  • eng

Conference Location

  • United States