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Blood, 1 August 2004, Vol. 104, No. 3, pp. 873-880.
Prepublished online as a Blood First Edition Paper on March 30, 2004; DOI 10.1182/blood-2003-11-3910.
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Submitted November 14, 2003
Accepted March 10, 2004
Matching at the MHC Class I K locus is essential for long-term engraftment of purified hematopoietic stem cells: a role for host NK cells in regulating HSC engraftment
Yiming Huang, Francine Rezzoug, Paula M Chilton, H L Grimes, Daniel E Cramer, and Suzanne T Ildstad*
Institute for Cellular Therapeutics, University of Louisville, Louisville, KY, USA
* Corresponding author; email: suzanne.ildstad{at}louisville.edu.
The events that regulate engraftment and long-term repopulating ability of hematopoietic stem cells (HSC) after transplantation are not well defined. We report for the first time that MHC Class I K plays a critical role in HSC engraftment via interaction with recipient NK cells. Durable engraftment of purified HSC requires MHC Class I K matching between HSC donor and recipient. In the absence of MHC Class I K matching, HSC exhibit impaired long-term engraftment (P = 0.01). Dependence on MHC Class I K matching is eliminated in B6 beige mice which lack NK cell function, as well as in wild type mice depleted of NK cells, implicating a possible regulatory role of NK cells for HSC engraftment. The co-administration of CD8+/TCR- graft facilitating cells (FC) matched at MHC Class I K to the HSC donor overcomes the requirement for MHC Class I K matching between HSC and recipient. These data demonstrate that FC inhibit NK cell effects on the HSC. Notably, FC do not suppress the cytotoxic activity of activated NK cells. EGFP+ FC persist for 1 month following allogeneic transplantation, making cold target inhibition an unlikely mechanism. Therefore, MHC Class I may play a critical role in the initiating events that dictate HSC engraftment and/or NK-mediated rejection following allogeneic transplantation.
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