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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0901807v1 183/9/5449    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Tabayoyong, W. B. Articles by Zavazava, N. PubMed PubMed Citation Articles by Tabayoyong, W. B. Articles by Zavazava, N.

HOXB4-Transduced Embryonic Stem Cell-Derived Lin^–c-kit⁺ and Lin^–Sca-1⁺ Hematopoietic Progenitors Express H60 and Are Targeted by NK Cells¹

William B. Tabayoyong,^* Juan G. Salas, Sabrina Bonde, and Nicholas Zavazava^2*

^*Medical Scientist Training Program and Immunology Graduate Program, University of Iowa, Iowa City, Iowa 52242; and Department of Internal Medicine, University of Iowa and Veteran Affairs Medical Center, Iowa City, Iowa 52246

Embryonic stem (ES) cells are a novel source of cells, especially hematopoietic progenitor cells that can be used to treat degenerative diseases in humans. However, there is a need to determine how ES cell-derived progenitors are regulated by both the adaptive and innate immune systems post transplantation. In this study, we demonstrate that hematopoietic progenitor cells (HPCs) derived from mouse ES cells ectopically expressing HOXB4 fail to engraft long-term in the presence of NK cells. In particular, the H60-expressing Lin^–c-kit⁺ and Lin^–Sca-1⁺ subpopulations were preferentially deleted in Rag2^–/–, but not in Rag2^–/–_c^–/– mice. Up-regulation of class I expression on HPCs prevented their lysis by NK cells, and Ab-mediated depletion of NK cells restored long-term HPC engraftment. In contrast to the notion that ES-derived cells are immune-privileged, we show in this study that NK cells form a formidable barrier to the long-term engraftment of ES cell-derived hematopoietic progenitors.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by National Institutes of Health R01 HL073015 and Veteran Affairs Merit Review.

² Address correspondence and reprint requests to Dr. Nicholas Zavazava, University of Iowa Hospitals and Clinics, Department of Internal Medicine, 200 Hawkins Drive, C42 E6 GH, Iowa City, Iowa 52242. E-mail address: nicholas-zavazava{at}uiowa.edu

³ Abbreviations used in this paper: ES cell, embryonic stem cell; EB, embryoid body; HPC, hematopoietic progenitor cell.

⁴ The online version of this article contains supplementary material.