Hybrid resistance to parental bone marrow grafts in nonlethally irradiated mice
| Autor: | Svenja Maschke, Thomas Wekerle, Mario Wiletel, Nina Pilat, Nicolas Granofszky, Moritz Muckenhuber, Benedikt Mahr, Karin Hock |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
basic (laboratory) research/science
Graft Rejection Male NK cell activation Hybrid Resistance 030230 surgery Brief Communication 03 medical and health sciences Mice 0302 clinical medicine Bone Marrow Immune Tolerance Immunology and Allergy Medicine natural killer (NK) cells/NK receptors Animals Pharmacology (medical) bone marrow/hematopoietic stem cell transplantation Lymph node innate immunity immunobiology Bone Marrow Transplantation animal models: murine Transplantation Mice Inbred BALB C Transplantation Chimera Innate immune system business.industry Hematopoietic stem cell tolerance: chimerism Killer Cells Natural Mice Inbred C57BL medicine.anatomical_structure Immunology Female Bone marrow Missing self rejection business Brief Communications |
| Zdroj: | American Journal of Transplantation |
| ISSN: | 1600-6143 1600-6135 |
| Popis: | 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. Modifying conditioning in the hybrid resistance model reveals that lasting chimerism ensues after nonmyeloablative irradiation, even when no recipient irradiation is given, indicating that natural killer cell–mediated bone marrow rejection is incomplete in reduced conditioning settings. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text