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Precursors inflammatory lymphids isolation/uses

CXCR4DNAM-1(CD226)HIVinflammation / autoimmunityNK/T cell

Introduction

The present invention refers to the identification of a novel cell population of human lymphoid progenitors characterized by the expression of markers such as CD34, DNAM-1(CD226) and CXCR4, to the method for their identification and to the uses in the therapeutic and diagnostic field. The percentage of the aforementioned population in the peripheral blood correlates with the chronic inflammation.

Technical features

CD34+DNAM-1bright CXCR4+ cell population occurs in the peripheral blood of patients affected by acute and chronic inflammation in percentages ranging from 1 to 20% while it is absent in the peripheral blood of healthy subjects or in general without chronic inflammatory pathology as well as in the umbilical cord blood. In flowcytometric analysis, the population in question is characterized by the simultaneous expression on the surface of the following markers:

  • CD34, DNAM-1 (CD226), CXCR4, CD69, CD38, HLA-DR;
  • While it does not exhibit expression of CD3, CD14, CD19, CD16, CD56, CD117, CDW328 (P75/ AIRM1), CD161, CCR7, CD11C, CD123;
  • Molecular biology analysis shows expression of the following transcription factors Id2, E4BP4, T-bet and Fox-P3;
  • Does not express GATA-3 transcription factor.

If cultured in vitro at 37 °C, 5% Co2 in a culture medium consisting of Myelocult medium, AB human serum, human recombinant IL7, human recombinant IL15, human recombinant FLT3-L, human recombinant SCF gives simultaneously rise to NK cells and CD4, CD8 and gd T cells.

Possible Applications

  • New inflammation marker;
  • Peripheral lymphoid cell turnover marker;
  • New therapies to autoimmune and neoplastic diseases/inflammatory conditions;
  • Control/prevention of GVHD development/CMV reactivation;
  • Immunotherapy with CAR-precursors/factories.

Advantages

  • Novel precursors give rise to progenies belonging to the innate and adaptive compartment of the human immune system;
  • Become an object of drug therapy development or itself have therapeutic potential;
  • Indicate a therapeutic diagnostic tool in T lymphocyte-mediated autoimmunity.