Introduction

The CD56-CD16+Perfneg precursor purified from PB of patients with HIV or HCV (Hepatitis C) infection, or experiencing Cytomegalovirus (CMV) reactivation after HSC transplantation, differentiated in vitro into CD94/NKG2C+KIR+CD57+ functional NK cell progenies that displayed strong selective HCMV-inhibiting activity in vitro. 347 genes were observed differentially expressed resulted in new and original invention.

Technical features

The CD56^–CD16⁺Perf^neg cell population occurs in the peripheral blood of the infected patients in percentages ranging from 1 to 20% while it is <1% in the peripheral blood of healthy subjects or generally without chronic inflammatory pathology as well as in the umbilical cord blood.

In flow cytometric analysis, the population in question is characterized by the simultaneous expression on the surface of the following markers:

• CD16;
• It does not show expression of CD3, CD14, CD19, CD16, CD56, Perforin;
• In vitro cultured at 37 ° C 5% Co2 in a culture medium constitutes of Myelocult medium, AB human serum, human recombinant IL7, human recombinant IL15, human recombinant FLT3-L, human recombinant SCF in the presence of cell line 221E after about 20 days it gives rise simultaneously to CD94 / NKG2C + KIR + CD57 + NK cells and CD4, CD8 T cells. It does not give rise to a myelomonocyte population so the progeny is CD33 negative;
• The progeny is able to inhibit the replication of HCMV  (Human cytomegalovirus);
• The NK CD94/NKG2C+KIR+CD57+ progeny has differentially expressed 347 transcripts with respect to the mature NK NKG2C + population present in the peripheral blood.

Possible Applications

• Development of pharmacological projects:
  • Aimed at controlling HCMV replication in patients undergoing stem cell transplantation;
  • Anti-viral activity;
  • Cytotoxic activity;
  • Modulators of IFNg production.

Advantages

• NK / NKG2C + progeny shows impact on HCMV replication control in transplantation:
  • Innovation in the field of hematopoietic stem cells
• Development of drug therapy in control HCMV replication in patients with defect in T-cell mediated immune response or in patients undergoing stem cell transplantation.