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Hybrid resistance to parental bone marrow grafts in nonlethally irradiated mice
Author(s) -
Mahr Benedikt,
Pilat Nina,
Granofszky Nicolas,
Wiletel Mario,
Muckenhuber Moritz,
Maschke Svenja,
Hock Karin,
Wekerle Thomas
Publication year - 2019
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.15146
Subject(s) - medicine , bone marrow transplantation , bone marrow , bone transplantation , pathology , surgery
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 (C57 BL 6 × BALB /c) recipient mice received titrated doses (5‐20 x 10 6 ) 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.