Selective growth advantage of wild-type lymphocytes in X-linked SCID recipients View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2002-07-01

AUTHORS

A Kume, M Koremoto, H Mizukami, T Okada, Y Hanazono, K Sugamura, K Ozawa

ABSTRACT

The cytokine receptor common gamma chain (γc) plays a pivotal role in multiple interleukin signaling, and γc gene mutations cause an X-linked form of SCID (X-SCID). Recently, γc gene transfer into the autologous X-SCID BM achieved appreciable lymphocyte reconstitution, contrasting with the limited success in previous gene therapy trials targeting hematopoietic stem cells. To understand the mechanisms underlying this success, we examined the repopulating potential of the wild-type (WT) BM cells using an X-SCID mouse model. Limited numbers of WT cells were infused into non-ablated WT and X-SCID hosts. Whereas no appreciable engraftment was observed in WT recipients, donor-derived lymphocytes repopulated well in X-SCID, reaching 37% (106cells given) and 53% (107 cells given) of the normal control value 5 months post BMT. A lineage analysis showed a predominance of the donor-derived lymphocytes (CD4+ T, CD8+ T, B and NK cells) in X-SCID while the donor-derived granulocytes and monocytes engrafted poorly. These results showed a selective advantage of WT cells in X-SCID, and that the advantage was restricted to lymphocytes. In human gene therapy for X-SCID, an analogous growth advantage would greatly enhance the repopulation of lymphocytes derived from a very small number of γc gene-supplemented precursors. More... »

PAGES

113-118

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.bmt.1703613

DOI

http://dx.doi.org/10.1038/sj.bmt.1703613

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1039110524

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12132050


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