The early expansion of anergic NKG2Apos/CD56dim/CD16neg natural killer cells represents a therapeutic target in haploidentical haematopoietic stem cell transplantation
- Creators
- Roberto, Alessandra
- Di Vito, Clara
- Zaghi, Elisa
- Mazza, Emilia Maria Cristina
- Capucetti, Arianna
- Calvi, Michela
- Tentorio, Paolo
- Zanon, Veronica
- Sarina, Barbara
- Mariotti, Jacopo
- Bramanti, Stefania
- Tenedini, Elena
- Tagliafico, Enrico
- Bicciato, Silvio
- Santoro, Armando
- Roederer, Mario
- Marcenaro, Emanuela
- Castagna, Luca
- Lugli, Enrico
- Mavilio, Domenico
- Others:
- Roberto, Alessandra
- Di Vito, Clara
- Zaghi, Elisa
- Mazza, Emilia Maria Cristina
- Capucetti, Arianna
- Calvi, Michela
- Tentorio, Paolo
- Zanon, Veronica
- Sarina, Barbara
- Mariotti, Jacopo
- Bramanti, Stefania
- Tenedini, Elena
- Tagliafico, Enrico
- Bicciato, Silvio
- Santoro, Armando
- Roederer, Mario
- Marcenaro, Emanuela
- Castagna, Luca
- Lugli, Enrico
- Mavilio, Domenico
Description
Natural Killer cells are the first lymphocyte population to reconstitute early after non myelo-ablative and T cell-replete haploidentical hematopoietic stem cell transplantation with post-transplant infusion of cyclophosphamide. The present study characterizes the transient and predominant expansion starting from the 2nd week after haploidentical hematopoietic stem cell transplantation of a donor-derived unconventional subset of NKp46neg-low/CD56dim/CD16neg natural killer cells expressing remarkable high levels of CD94/NKG2A. Both transcription and phenotypic profiles indicated that unconventional NKp46neg-low/CD56dim/CD16neg natural killer cells are a distinct natural killer cell subpopulation with features of late stage differentiation, yet retaining proliferative capability and functional plasticity to generate conventional NKp46pos/CD56bright/CD16pos natural killer cells in response to interleukin-15 plus interleukin-18. While present at low frequency in healthy donors, unconventional NKp46neg-low/CD56dim/CD16neg natural killer cells are greatly expanded in the following 7 weeks after haploidentical hematopoietic stem cell transplantation and express high levels of the activating receptors NKGD and NKp30 as well as of the lytic granules Granzyme-B and Perforin. Nonetheless, NKp46neg-low/CD56dim/CD16neg natural killer cells displayed a markedly defective cytotoxicity that could be reversed by blocking the inhibitory receptor CD94/NKG2A. These data open new important perspectives to better understand the ontogenesis/homeostasis of human natural killer cells and to develop a novel immune-therapeutic approach that targets the inhibitory NKG2A check point, thus unleashing natural killer cell alloreactivity early after haploidentical hematopoietic stem cell transplantation.
Additional details
- URL
- http://hdl.handle.net/11567/908661
- URN
- urn:oai:iris.unige.it:11567/908661
- Origin repository
- UNIGE