Immunologic potential of donor lymphocytes expressing a suicide gene for early immune reconstitution after hematopoietic T-cell-depleted stem cell transplantation

Blood. 2003 Feb 15;101(4):1290-8. doi: 10.1182/blood-2002-08-2351. Epub 2002 Oct 3.


We have previously shown that the infusion of donor lymphocytes expressing the herpes simplex virus thymidine kinase (HSV-tk) gene is an efficient tool for controlling graft-versus-host disease (GVHD) while preserving the graft-versus-leukemia (GVL) effect. In addition to the GVL effect, the administration of donor HSV-tk(+) cells could have a clinical impact in promoting immune reconstitution after T-cell-depleted stem cell transplantation (SCT). To explore this hypothesis, we have investigated whether in vitro polyclonal activation, retroviral transduction, immunoselection, and expansion affect the immune competence of donor T cells. We have observed that, after appropriate in vitro manipulation, T cells specific for antigens relevant in the context of SCT are preserved in terms of frequency, expression of T-cell receptor, proliferation, cytokine secretion, and lytic activity. A reduction in the frequency of allospecific T-cell precursors is observed after prolonged T-cell culture, suggesting that cell manipulation protocols involving a short culture time and high transduction efficiency are needed. Finally, the long-term persistence of HSV-tk(+) cells was observed in a patient treated in the GVL clinical trial, and a reversion of the phenotype of HSV-tk(+) cells from CD45RO(+) to CD45RA(+) was documented more than 2 years after the infusion. Based on all this evidence, we propose a clinical study of preemptive infusions of donor HSV-tk(+) T cells after SCT from haploidentical donors to provide early immune reconstitution against infection and potential immune protection against disease recurrence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Viral / immunology
  • Blood Donors
  • Cells, Cultured
  • Cytomegalovirus / immunology
  • Graft vs Host Disease / prevention & control
  • Graft vs Leukemia Effect
  • Herpesvirus 4, Human / immunology
  • Humans
  • Immunophenotyping
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / biosynthesis
  • Isoantigens / immunology
  • Leukocyte Common Antigens / analysis
  • Lymphocyte Depletion
  • Lymphocyte Subsets
  • Lymphocyte Transfusion*
  • Lymphocytes / enzymology*
  • Lymphocytes / immunology
  • Retroviridae / genetics
  • Simplexvirus / enzymology
  • Stem Cell Transplantation*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Cytotoxic / immunology
  • Thymidine Kinase / genetics*
  • Transfection


  • Antigens, Viral
  • Interleukin-2
  • Isoantigens
  • Interferon-gamma
  • Thymidine Kinase
  • Leukocyte Common Antigens