Differential expression of THELPER 1 cytokines upon antigen stimulation predicts ex vivo proliferative potential and cytokine production of virus-specific T cells following re-stimulation

Transpl Infect Dis. 2014 Oct;16(5):713-23. doi: 10.1111/tid.12281. Epub 2014 Sep 9.


Introduction: Cytomegalovirus (CMV) and human adenovirus (ADV) infections are causes of morbidity after stem cell transplantation. Antigen (Ag)-specific T cells are essential for the control of viral infections. However, in vivo expansion potential of T-cell subpopulations is hardly predictable in humans. Furthermore, ex vivo identification of human T cells with repopulating capacity for adoptive T-cell transfer has been difficult.

Methods: We analyzed Ag-specific T-cell populations, subdivided according to the expression of different THELPER- 1 (Th1) cytokines. Isolation by flow cytometry was based on interferon-gamma (IFN)-γ, interleukin (IL)-2, or tumor necrosis factor-alpha (TNF-α) secretion of T cells after ex vivo stimulation with the Ags hexon (for ADV) and pp65 (for CMV). Isolated T cells were expanded and examined for functional characteristics, expansion/differentiation potential, and naïve, effector memory, central memory, and late effector phenotypes.

Results: Isolation based on IFN-γ production provides a T-cell population with a mixture of early, central memory, and effector memory T cells, high expansion potential, and effective cytokine production. Selection of T cells with Ag-specific expression of IL-2 or TNF-α, however, results in a T-cell population with reduced proliferation and lower effector potential after expansion.

Conclusion: We conclude that the exclusive secretion of IFN-γ in the human antiviral T-cell responses preferentially leads to higher repopulation capacities of antiviral T cells, compared to IL-2 or TNF-α secreting T-cell populations.

Keywords: Th1 cytokines; adenovirus; adoptive T-cell transfer; cytomegalovirus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • CD8-Positive T-Lymphocytes* / chemistry
  • Capsid Proteins / immunology
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Humans
  • Immunologic Memory
  • Interferon-gamma / analysis
  • Interferon-gamma / metabolism*
  • Interleukin-2 / analysis
  • Interleukin-2 / metabolism*
  • L-Selectin / analysis
  • Leukocyte Common Antigens / analysis
  • Lymphocyte Count
  • Phosphoproteins / immunology
  • Th1 Cells / chemistry
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism*
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / metabolism*
  • Viral Matrix Proteins / immunology


  • Capsid Proteins
  • Interleukin-2
  • Phosphoproteins
  • Tumor Necrosis Factor-alpha
  • Viral Matrix Proteins
  • cytomegalovirus matrix protein 65kDa
  • hexon capsid protein, Adenovirus
  • L-Selectin
  • Interferon-gamma
  • Leukocyte Common Antigens