Establishment of a healthy human range for the whole blood "OX40" assay for the detection of antigen-specific CD4+ T cells by flow cytometry

Cytometry B Clin Cytom. 2014 Sep;86(5):350-61. doi: 10.1002/cyto.b.21165. Epub 2014 May 14.

Abstract

Background: Clinical investigation of antigen-specific T cells in potentially immunodeficient patients is an important and often challenging aspect of patient diagnostic work up. Methods for detection of microbial exposure to the T-cell compartment exist but are laborious and time consuming. Recently, a whole blood technique involving flow cytometry and detection of CD25 and OX40 (CD134) expression on the surface of activated CD4+ T cells was shown to be accurate and concordant when compared with more traditional methods of antigen-specific T-cell detection.

Methods: Whole heparinized blood was collected from healthy donors and set up using the "OX40" assay to detect antigen-specific CD4+ T-cell responses to Varicella Zoster Virus, Epstein-Barr Virus (EBV), Cytomegalovirus, Candida albicans, and Streptococcus pneumoniae.

Results: The "OX40" assay technique was clinically validated for routine use in an NHS clinical immunology laboratory by analysis of incubation length (40-50 h), sample transport time (up to 24 h at room temperature), concordance with serology testing, proliferation and interferon-gamma production. In addition, 63 healthy controls (age range 21-78) were tested for responses to generate a healthy control reference range.

Conclusions: The OX40 assay, as presented in this report, represents an economical, rapid, robust whole blood technique to detect antigen-specific T cells, which is suitable for clinical immunology diagnostic laboratory use.

Keywords: CD4+ T cells; costimulation/costimulatory; diagnostics; flow cytometry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CD4-Positive T-Lymphocytes / immunology*
  • Candida albicans / immunology
  • Cytomegalovirus / immunology
  • Female
  • Flow Cytometry / methods
  • Herpesvirus 3, Human / immunology
  • Herpesvirus 4, Human / immunology
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-2 Receptor alpha Subunit / analysis*
  • Male
  • Middle Aged
  • Receptors, OX40 / analysis*
  • Reference Values
  • Streptococcus pneumoniae / immunology
  • Young Adult

Substances

  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • Receptors, OX40
  • TNFRSF4 protein, human
  • Interferon-gamma