Adenovirus-specific T-lymphocyte efficacy in the presence of methylprednisolone: An in vitro study

Cytotherapy. 2018 Apr;20(4):524-531. doi: 10.1016/j.jcyt.2017.12.010. Epub 2018 Mar 1.

Abstract

Virus-specific T-cell (VST) infusion becomes a promising alternative treatment for refractory viral infections after hematopoietic stem cell transplantation (HSCT). However, VSTs are often infused during an immunosuppressive treatment course, especially corticosteroids, which are a first-line curative treatment of graft-versus-host disease (GVHD). We were interested in whether corticosteroids could affect adenovirus (ADV)-VST functions. After interferon (IFN)-γ based immunomagnetic selection, ADV-VSTs were in vitro expanded according to three different culture conditions: without methylprednisolone (MP; n = 7), with a final concentration of MP 1 µg/mL (n = 7) or MP 2 µg/mL (n = 7) during 28 ± 11 days. Efficacy and alloreactivity of expanded ADV-VSTs was controlled in vitro. MP transitorily inhibited ADV-VST early expansion. No impairment of specific IFN-γ secretion capacity and cytotoxicity of ADV-VSTs was observed in the presence of MP. However, specific proliferation and alloreactivity of ADV-VSTs were decreased in the presence of MP. Altogether, these results and the preliminary encouraging clinical experiences of co-administration of MP 1 mg/kg and ADV-VSTs will contribute to safe and efficient use of anti-viral immunotherapy.

Keywords: adenovirus-specific T lymphocyte; interferon-γ–based immunomagnetic isolation; methylprednisolone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / immunology*
  • Adenoviridae Infections / immunology
  • Adenoviridae Infections / therapy
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Immunomagnetic Separation / methods
  • Immunotherapy
  • Interferon-gamma / chemistry
  • Interferon-gamma / metabolism
  • Methylprednisolone / pharmacology*
  • T-Cell Antigen Receptor Specificity / drug effects*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / physiology
  • Virus Diseases / immunology
  • Virus Diseases / therapy

Substances

  • Interferon-gamma
  • Methylprednisolone