Abstract
Resistance to parental bone marrow (BM) grafts in F1 hybrid recipients is due to natural killer (NK) cell–mediated rejection triggered through “missing self” recognition. “Hybrid resistance” has usually been investigated in lethally irradiated F1 recipients in conjunction with pharmacological activation of NK cells. Here, we investigated BM‐directed NK‐cell alloreactivity in settings of reduced conditioning. Nonlethally irradiated (1‐3 Gy) or nonirradiated F1 (C57BL6 × BALB/c) recipient mice received titrated doses (5‐20 x 106) of unseparated parental BALB/c BM without pharmacological NK cell activation. BM successfully engrafted in all mice and multilineage donor chimerism persisted long‐term (24 weeks), even in the absence of irradiation. Chimerism was associated with the rearrangement of the NK‐cell receptor repertoire suggestive of reduced reactivity to BALB/c. Chimerism levels were lower after transplantation with parental BALB/c than with syngeneic F1 BM, indicating partial NK‐mediated rejection of parental BM. Activation of NK cells with polyinosinic–polycytidylic acid sodium salt poly(I:C), reduced parental chimerism in nonirradiated BM recipients but did not prevent hematopoietic stem cell engraftment. In contrast, equal numbers of parental lymph node cells were completely rejected. Hence, hybrid resistance leads to incomplete rejection of parental BM under reduced conditioning settings.
Highlights
Natural killer (NK) cells are large granular lymphocytes that serve as first‐line defense against pathogens and neoplastic cells.[1]
The results presented reveal that under reduced condition‐ ing settings, parental bone marrow (BM) is only partially rejected by NK cells in F1 recipients
Multi‐lineage chimerism ensues even in nonirradiated F1 recipients transplanted with moderate BM doses
Summary
Natural killer (NK) cells are large granular lymphocytes that serve as first‐line defense against pathogens and neoplastic cells.[1]. It is widely acknowledged that NK cells play a major role in the rejec‐ tion of allogeneic bone marrow (BM), they are not able to fully reject solid allografts.[2,3] The importance of NK cells in the rejection of allogeneic BM cells has been elegantly demonstrated when parental BM was transplanted into the first generation (F1) of offspring recipients (“hybrids”).[4] Under these circumstances.
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