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

Stem Cells. 2007 Feb;25(2):537-42. doi: 10.1634/stemcells.2006-0319. Epub 2006 Oct 5.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology*
  • Antigens, CD34 / immunology*
  • Bone Marrow
  • Cell Differentiation*
  • Child
  • Child, Preschool
  • Epitopes / immunology*
  • Flow Cytometry
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Infant
  • Leukocyte Common Antigens / immunology
  • Mice
  • Mice, SCID
  • Receptors, Antigen, T-Cell / biosynthesis
  • Stem Cells / cytology*
  • Stem Cells / immunology*
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology
  • Thymus Gland / cytology

Substances

  • Antibodies
  • Antigens, CD34
  • Epitopes
  • Receptors, Antigen, T-Cell
  • Leukocyte Common Antigens