Natural killer cell crosstalk with allogeneic human cardiac-derived stem/progenitor cells controls persistence. (11th September 2014)

• Record Type: Journal Article
• Authors: Boukouaci, Wahid; Lauden, Laura; Siewiera, Johan; Dam, Noemie; Hocine, Hocine-Rachid; Khaznadar, Zena; Tamouza, Ryad; Borlado, Luis R.; Charron, Dominique; Jabrane-Ferrat, Nabila; Al-Daccak, Reem
• Is Part Of: Cardiovascular research. Volume 104:Number 2(2015)
• Page Start: 290
• Page End: 302
• Publication Date: 2014-09-11
• Subjects: Human cardiac stem/progenitor cells -- Myocardial infarction -- Allogenicity -- NK cells; Cardiovascular system -- Diseases -- Periodicals; Cardiovascular system -- Periodicals; 616.1
• DOI: 10.1093/cvr/cvu208
• Languages: English
• ISSNs: 0008-6363

Abstract

Abstract: Aims: Allogeneic human cardiac-derived stem/progenitor cells (hCPC) are promising candidates for cardiac repair. They interact with T cells, major effectors of the adaptive immune response, inducing 'paracrine' anti-inflammatory effects that could sustain tissue repair/regeneration. Natural killer (NK) cells are major effectors of the innate immune system that might influence the persistence of therapeutic stem/progenitor cells. Therefore, to get through successful clinical translation and anticipate allogeneic hCPC persistence, we defined their crosstalk with NK cells under steady state and inflammatory conditions. Methods and results: By using an experimental model of allogeneic hCPC/NK cell interaction, we demonstrate that hCPC moderately trigger cytokine-activated, but not resting, NK cell killing that occurs through formation of lytic immunological synapse and NK cell natural cytotoxicity. Yet, inflammatory context substantially decreases their capacity to set cytokine-activated NK cell functions towards NK cell-cytotoxicity and protects hCPC from NK cell killing. Allogeneic hCPC also restrain NK cell-cytotoxicity against conventional targets and inflammatory cytokine secretion biasing the latter towards anti-inflammatory cytokines. Thus, hCPC are unprivileged targets for allogeneic NK cells and can restrain NK cell functions in allogeneic setting. Conclusion: Collectively, our data suggest that allogeneic hCPC/innate NK cells crosstalk within injured inflamed myocardium would permit their retention and might contribute to attenuating inflammation and to preventing adverse cardiac remodelling.