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Cardiovasc Res. 2014 Nov 1;104(2):290-302. doi: 10.1093/cvr/cvu208. Epub 2014 Sep 11.

Natural killer cell crosstalk with allogeneic human cardiac-derived stem/progenitor cells controls persistence.

Author information

1
Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS940, Institut Universitaire d'Hématologie, Université Paris-Diderot and Laboratoire d'Immunologie et d'Histocompatibilité, Transplantex, Hôpital Saint Louis, CIB-HOG, AP-HP, Batiment Bazin, 1 Avenue Claude Vellefaux, Paris 75010, France.
2
INSERM UMR 1043 and CNRS UMR 5282, University Toulouse III Paul Sabatier, Toulouse, France.
3
Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS940, Institut Universitaire d'Hématologie, Université Paris-Diderot and Laboratoire d'Immunologie et d'Histocompatibilité, Transplantex, Hôpital Saint Louis, CIB-HOG, AP-HP, Batiment Bazin, 1 Avenue Claude Vellefaux, Paris 75010, France Coretherapix S.L., Madrid, Spain.
4
Coretherapix S.L., Madrid, Spain.
5
Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS940, Institut Universitaire d'Hématologie, Université Paris-Diderot and Laboratoire d'Immunologie et d'Histocompatibilité, Transplantex, Hôpital Saint Louis, CIB-HOG, AP-HP, Batiment Bazin, 1 Avenue Claude Vellefaux, Paris 75010, France reem.al-daccak@inserm.fr.

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.

KEYWORDS:

Allogenicity; Human cardiac stem/progenitor cells; Myocardial infarction; NK cells

PMID:
25213554
DOI:
10.1093/cvr/cvu208
[Indexed for MEDLINE]

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