Donor-derived CD4(+)/CCR7(+) T-cell partial selective depletion does not alter acquired anti-infective immunity

Bone Marrow Transplant. 2014 May;49(5):611-5. doi: 10.1038/bmt.2014.6. Epub 2014 Feb 24.

Abstract

In previous studies, we observed that a high proportion of donor-derived CD4(+) T cells expressing the chemokine receptor 7 (CCR7) was a major determinant of acute GVHD, without interfering with the incidence of other post-transplant outcomes, especially relapse and nonrelapse mortality rates. Here, we investigated in vitro the impact of partially selective CD4(+)/CCR7(+) T lymphocytes on acquired anti-infective immune response in 10 donors who underwent G-CSF-primed PBSC collection. Similar quantitative and functional proliferative reactions were observed in lymphocyte cultures in the presence of adenovirus and pp65 Ags with unmanipulated and partially depleted donor samples. No responses were observed in the presence of human T-cell lymphotropic virus type 1 used as a negative control. These results complete the proof of concept needed to build a clinical trial investigating partially selective CD4(+)/CCR7(+) T cell-depleted allo-SCT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Bone Marrow Transplantation / adverse effects
  • Bone Marrow Transplantation / methods
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / transplantation*
  • Cell Proliferation
  • Cell Separation / methods*
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Flow Cytometry / methods
  • Fluoresceins
  • Fluorescent Dyes
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / prevention & control*
  • Hematologic Neoplasms / therapy
  • Humans
  • Interferon-gamma / metabolism
  • Lymphocyte Depletion / methods*
  • Lymphocyte Transfusion / adverse effects
  • Lymphocyte Transfusion / methods*
  • Male
  • Receptors, CCR7 / metabolism*
  • Succinimides
  • Tissue Donors
  • Tritium

Substances

  • 5-(6)-carboxyfluorescein diacetate succinimidyl ester
  • CCR7 protein, human
  • Fluoresceins
  • Fluorescent Dyes
  • Receptors, CCR7
  • Succinimides
  • Tritium
  • Interferon-gamma