Analysis of memory-like natural killer cells in human cytomegalovirus-infected children undergoing αβ+T and B cell-depleted hematopoietic stem cell transplantation for hematological malignancies.

نویسندگان

  • Letizia Muccio
  • Alice Bertaina
  • Michela Falco
  • Daniela Pende
  • Raffaella Meazza
  • Miguel Lopez-Botet
  • Lorenzo Moretta
  • Franco Locatelli
  • Alessandro Moretta
  • Mariella Della Chiesa
چکیده

We analyzed the impact of human cytomegalovirus infection on the development of natural killer cells in 27 pediatric patients affected by hematological malignancies, who had received a HLA-haploidentical hematopoietic stem cell transplantation, depleted of both α/β+ T cells and B cells. In line with previous studies in adult recipients of umbilical cord blood transplantation, we found that human cytomegalovirus reactivation accelerated the emergence of mature natural killer cells. Thus, most children displayed a progressive expansion of a memory-like natural killer cell subset expressing NKG2C, a putative receptor for human cytomegalovirus, and CD57, a marker of terminal natural killer cell differentiation. NKG2C(+)CD57(+) natural killer cells were detectable by month 3 following hematopoietic stem cell transplantation and expanded until at least month 12. These cells were characterized by high killer Ig-like receptors (KIRs) and leukocyte inhibitory receptor 1 (LIR-1) and low Siglec-7, NKG2A and Interleukin-18Rα expression, killed tumor targets and responded to cells expressing HLA-E (a NKG2C ligand). In addition, they were poor Interferon-γ producers in response to Interleukin-12 and Interleukin-18. The impaired response to these cytokines, together with their highly differentiated profile, may reflect their skewing toward an adaptive condition specialized in controlling human cytomegalovirus. In conclusion, in pediatric patients receiving a type of allograft different from umbilical cord blood transplantation, human cytomegalovirus also induced memory-like natural killer cells, possibly contributing to controlling infections and reinforcing anti-leukemia effects.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

بهبود بقا بیماران مبتلا به لوسمی لنفوبلاستیک حاد فاقد HLA-A3/11 برای KIR3DL2 دهنده پس از پیوند سلول های بنیادی خونساز از خواهر یا برادر با HLA مشابه بدون تخلیه سلول T

A potential factor influencing hematopoietic stem cells transplantation (HSCT) outcome is the presence of donor-derived alloreactive natural killer (NK) cells. This retrospective analysis studied the impact of NK alloreactivity based on the missing KIR ligand, for acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) patients undergoing non-T-cell depleted HLA-identical sibling HS...

متن کامل

Invariant natural killer T cells reconstitution and the control of leukemia relapse in pediatric haploidentical hematopoietic stem cell transplantation

CD1d-restricted invariant (i)NKT cells are innate-like, lipid-reactive T lymphocytes implicated in the control of infections, cancer and autoimmunity. Our study suggests that the reconstitution of the peripheral iNKT cell compartment, following HLA-haploidentical hematopoietic stem cell transplantation, associates with leukemia control in children affected by different hematological malignancies.

متن کامل

Relation between Age, Gender, Number of Blood Products Received and Diagnosis with Engraftment and Length of Hospital Stay in Patients Undergoing Autologous Stem Cell Transplantation

Background and purpose: Autologous hematopoietic stem cell transplantation may be one of the best treatment options for some patients with hematological malignancies. The process of stem cell homing in the bone marrow and the production and proliferation of denovo cell populations is called engraftment and could be considered as one of the key factors in the success of stem cell transplantation...

متن کامل

Impact of HCMV Infection on NK Cell Development and Function after HSCT

Natural Killer (NK) cell function is regulated by an array of inhibitory and activating surface receptors that during NK cell differentiation, at variance with T and B cells, do not require genetic rearrangement. Importantly, NK cells are the first lymphocyte population recovering after hematopoietic stem cell transplantation (HSCT). Thus, their role in early immunity after HSCT is considered c...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Haematologica

دوره 101 3  شماره 

صفحات  -

تاریخ انتشار 2016