Human T lymphocytes transduced by lentiviral vectors in the absence of TCR activation maintain an intact immune competence

Simona Cavalieri, Sabrina Cazzaniga, Massimo Geuna, Zulma Magnani, Claudio Bordignon, Luigi Naldini, Chiara Bonini

Research output: Contribution to journalArticlepeer-review

Abstract

Gene transfer into T lymphocytes is currently being tested for the treatment of lymphohematologic disorders. We previously showed that suicide gene transfer into donor lymphocytes infused to treat leukemic relapse after allogeneic hematopoietic stem cell transplantation allowed control of graft-versus-host disease. However, the T-cell receptor (TCR) activation and sustained proliferation required for retroviral vector transduction may impair the half-life and immune competence of transduced cells and reduce graft-versus-leukemia activity. Thus, we tested lentiviral vectors (LVs) and stimulation with cytokines involved in antigen-independent T-cell homeostasis, such as interleukin 7 (IL-7), IL-2, and IL-15. Late-generation LVs transduced efficiently nonproliferating T cells that had progressed from G0 to the G1 phase of the cell cycle on cytokine treatment. Importantly, IL-2 and IL-7, but not IL-15, stimulation preserved physiologic CD4/CD8 and naive-memory ratios in transduced cells with only minor induction of some activation markers. Functional analysis of immune response to cytomegalovirus (CMV) showed that, although CMV-specific T cells were preserved by all conditions of transduction, proliferation and specific killing of autologous cells presenting a CMV epitope were higher for IL-2 and IL-7 than for IL-15. Thus, LV transduction of IL-2 or IL-7 prestimulated cells overcomes the limitations of retroviral vectors and may significantly improve the efficacy of T-cell-based gene therapy.

Original languageEnglish
Pages (from-to)497-505
Number of pages9
JournalBlood
Volume102
Issue number2
DOIs
Publication statusPublished - Jul 15 2003

ASJC Scopus subject areas

  • Hematology

Fingerprint Dive into the research topics of 'Human T lymphocytes transduced by lentiviral vectors in the absence of TCR activation maintain an intact immune competence'. Together they form a unique fingerprint.

Cite this