The adaptive immune system depends on the efficient response of lymphocytes, protecting the organism from infection or malignant diseases. T-cell immunodeficiency, innate or acquired, put the patient at risk for developing opportunistic infections and cancers. We previously described a novel approach to overcome the major limitations of T-cell immunotherapy and hematopoietic stem cell transplant (HSCT) by transplanting human T-lymphoid progenitors (HTLP), with the aim to achieve shortened immune reconstitution and fully functional naïve T-cell repertoire in immunodeficient or immunocompromised patients. By complementing our DL4-based cell culture with TNFα we developed and scaledup clinical strategies involving hematopoietic stem and progenitor cells (HSPC) differentiated into T-lymphoid progenitors. We discuss here recent advances made in the characterization of different cell sources used as starting materials for T-lymphoid progenitors manufacturing, as well as gene modification of these cells, highlighting new perspectives for the development of therapeutical strategies.
Clinical immunology, Immune reconstitution, Immunodeficiency disorders, Immunotherapy, Stem cell, T-cell progenitors, Thymus, Transplantation immunology