Natural killer cell receptor repertoire following HLA-matched allogeneic hematopoietic stem cell transplantation

Abstract

6635 Background: Following hematopoietic stem cell transplantation (HSCT), natural killer (NK) cells are among the first lymphocytes to recover, returning to normal levels within six weeks after HSCT. NK cells may mediate anti-tumor effects and regulate graft versus host disease (GVHD); modulation of the relative frequency and intensity of expression of the cytotoxic NK receptors may influence NK activity post transplant. Methods: We compared the NK receptor expression in seven patients at one month following non-myeloablative HLA-matched allogeneic HSCT with that of donors and healthy volunteers. NK cells were divided into two subsets based on expression of CD56 and CD16. Both subsets were assessed for three main classes of receptors that trigger or inhibit cytotoxicity: natural cytotoxicity receptors (NCR), killer immunoglobulin-like receptors (KIR) and C-type lectin receptors. Results: Compared to donors, the expression of the NCR NKp46 increased significantly in all patients, whereas NKp30 increased in the CD 56+ bright subset only in patients that developed acute GVHD. Expression of KIR receptors (CD158A, CD158B) did not change or decreased slightly. In contrast the C-type lectin receptor CD 94 was upregulated on most NK cells. The heterodimeric partners of CD94, NKG2A and NKG2C, were also increased, but the increase in frequency of cells expressing the inhibitory receptor NKG2A was greater than that of the activating receptor NKG2C. The homodimeric activating receptor NKG2D increased in all patients. No significant differences in NK receptor expression between the donors and healthy volunteers was observed Conclusions: These results demonstrate changes in the NK receptor repertoire during the early post-transplant period that may have an impact on NK cells mediated cytotoxicity. No significant financial relationships to disclose.