In vivo alloreactive potential of ex vivo-expanded primary T lymphocytes

Emmanuel Contassot, William J Murphy, Régis Angonin, Jean Jacques Pavy, Marcelo C. Bittencourt, Éric Robinet, Craig W. Reynolds, Jean Yves Cahn, Patrick Hervé, Pierre Tiberghien

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53 Scopus citations

Abstract

Background. We are presently investigating the therapeutic potential of herpes simplex-thymidine kinase-expressing donor T cells in the setting of a T cell-depleted allogeneic bone marrow transplantation. The generation, expansion, and selection of the gene-modified T cells require a 12-day ex vivo culture period in high-dose interleukin (IL)-2 that could significantly alter their in vivo alloreactivity. Methods. We evaluated the alloreactive potential of such cultured cells in a murine allogeneic bone marrow transplantation model. Results. The present studies demonstrate that ex vivo- expanded cultured T cells are capable of strong alloreactivity as evidenced by the occurrence of lethal acute graft-versus-host disease (GVHD). However, GVHD mortality after administration of the cultured T cells occurred later than after the administration of a same number of fresh T cells. Similar kinetics of GVHD-induced mortality between cultured and fresh T cells required a 10-fold increase in the number of cultured T cells, indicating a reduced alloreactive potential of these cells. The addition of a 2-day 'resting' period in low-dose IL-2 resulted in T cells with enhanced alloreactive potential identical to the alloreactivity observed with fresh T cells. Conclusion. Ex vivo IL-2 expanded T cells are capable of significant in vivo alloreactivity. However, an increase in the number of cultured T cells administered or the introduction of a short resting culture period prior to infusion is necessary in order to achieve in vivo alloreactivity identical to the alloreactivity observed with fresh T cells.

Original languageEnglish (US)
Pages (from-to)1365-1370
Number of pages6
JournalTransplantation
Volume65
Issue number10
DOIs
StatePublished - May 27 1998
Externally publishedYes

ASJC Scopus subject areas

  • Transplantation
  • Immunology

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    Contassot, E., Murphy, W. J., Angonin, R., Pavy, J. J., Bittencourt, M. C., Robinet, É., Reynolds, C. W., Cahn, J. Y., Hervé, P., & Tiberghien, P. (1998). In vivo alloreactive potential of ex vivo-expanded primary T lymphocytes. Transplantation, 65(10), 1365-1370. https://doi.org/10.1097/00007890-199805270-00014