Favorable impact of natural killer cell reconstitution on chronic graft-versus-host disease and cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation
Vissal David Kheav,
Marc Busson,
Catherine Scieux,
Régis Peffault de Latour,
Guitta Maki,
Philippe Haas,
Marie-Christine Mazeron,
Maryvonnick Carmagnat,
Emeline Masson,
Aliénor Xhaard,
Marie Robin,
Patricia Ribaud,
Nicolas Dulphy,
Pascale Loiseau,
Dominique Charron,
Gérard Socié,
Antoine Toubert,
Hélène Moins-Teisserenc
Affiliations
Vissal David Kheav
Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, Laboratoire d’Immunologie et Histocompatibilité, Paris;Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d’Hématologie Paris;;INSERM UMRS-1160, Paris;
Marc Busson
Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d’Hématologie Paris;;INSERM UMRS-1160, Paris;
Catherine Scieux
Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d’Hématologie Paris;;AP-HP, Hôpital Saint-Louis, Laboratoire de Microbiologie, Paris, France
Régis Peffault de Latour
Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d’Hématologie Paris;;AP-HP, Hôpital Saint-Louis, Service d’Hématologie-Greffe de Moelle, Paris;
Guitta Maki
Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, Laboratoire d’Immunologie et Histocompatibilité, Paris
Philippe Haas
Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, Laboratoire d’Immunologie et Histocompatibilité, Paris;Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d’Hématologie Paris;;INSERM UMRS-1160, Paris;
Marie-Christine Mazeron
Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d’Hématologie Paris;;AP-HP, Hôpital Saint-Louis, Laboratoire de Microbiologie, Paris, France
Maryvonnick Carmagnat
Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, Laboratoire d’Immunologie et Histocompatibilité, Paris
Emeline Masson
Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, Laboratoire d’Immunologie et Histocompatibilité, Paris
Aliénor Xhaard
AP-HP, Hôpital Saint-Louis, Service d’Hématologie-Greffe de Moelle, Paris;
Marie Robin
AP-HP, Hôpital Saint-Louis, Service d’Hématologie-Greffe de Moelle, Paris;
Patricia Ribaud
AP-HP, Hôpital Saint-Louis, Service d’Hématologie-Greffe de Moelle, Paris;
Nicolas Dulphy
Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, Laboratoire d’Immunologie et Histocompatibilité, Paris;Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d’Hématologie Paris;;INSERM UMRS-1160, Paris;
Pascale Loiseau
Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, Laboratoire d’Immunologie et Histocompatibilité, Paris;INSERM UMRS-1160, Paris;
Dominique Charron
Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, Laboratoire d’Immunologie et Histocompatibilité, Paris;Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d’Hématologie Paris;
Gérard Socié
Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d’Hématologie Paris;;INSERM UMRS-1160, Paris;;AP-HP, Hôpital Saint-Louis, Service d’Hématologie-Greffe de Moelle, Paris;
Antoine Toubert
Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, Laboratoire d’Immunologie et Histocompatibilité, Paris;Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d’Hématologie Paris;;INSERM UMRS-1160, Paris;
Hélène Moins-Teisserenc
Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, Laboratoire d’Immunologie et Histocompatibilité, Paris;Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d’Hématologie Paris;;INSERM UMRS-1160, Paris;
Natural killer cells are the first lymphocyte subset to reconstitute, and play a major role in early immunity after allogeneic hematopoietic stem cell transplantation. Cells expressing the activating receptor NKG2C seem crucial in the resolution of cytomegalovirus episodes, even in the absence of T cells. We prospectively investigated natural killer-cell reconstitution in a cohort of 439 adult recipients who underwent non-T-cell-depleted allogeneic hematopoietic stem cell transplantation between 2005 and 2012. Freshly collected blood samples were analyzed 3, 6, 12 and 24 months after transplantation. Data were studied with respect to conditioning regimen, source of stem cells, underlying disease, occurrence of graft-versus-host disease, and profiles of cytomegalovirus reactivation. In multivariate analysis we found that the absolute numbers of CD56bright natural killer cells at month 3 were significantly higher after myeloablative conditioning than after reduced intensity conditioning. Acute graft-versus-host disease impaired reconstitution of total and CD56dim natural killer cells at month 3. In contrast, high natural killer cell count at month 3 was associated with a lower incidence of chronic graft-versus-host disease, independently of a previous episode of acute graft-versus-host disease and stem cell source. NKG2C+CD56dim and total natural killer cell counts at month 3 were lower in patients with reactivation of cytomegalovirus between month 0 and month 3, but expanded greatly afterwards. These cells were also less numerous in patients who experienced later cytomegalovirus reactivation between month 3 and month 6. Our results advocate a direct role of NKG2C-expressing natural killer cells in the early control of cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation.
