title: 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.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatric Hematology/Oncology, University Children's Hospital Tübingen, Tübingen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Feucht
authors.forename: J
authors.initials: J
authors.lastname: Leibold
authors.forename: A
authors.initials: A
authors.lastname: Halder
authors.forename: S
authors.initials: S
authors.lastname: Kayser
authors.forename: L
authors.initials: L
authors.lastname: Hartl
authors.forename: H-G
authors.initials: HG
authors.lastname: Rammensee
authors.forename: R
authors.initials: R
authors.lastname: Handgretinger
authors.forename: T
authors.initials: T
authors.lastname: Feuchtinger
mesh_terms: D056704:Adaptive Immunity; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry; D036022:Capsid Proteins / Q000276:immunology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000032:analysis / Q000378:metabolism*; D007376:Interleukin-2 / Q000032:analysis / Q000378:metabolism*; D019041:L-Selectin / Q000032:analysis; D017493:Leukocyte Common Antigens / Q000032:analysis; D018655:Lymphocyte Count; D010750:Phosphoproteins / Q000276:immunology; D018417:Th1 Cells / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: D036022:Capsid Proteins; D007376:Interleukin-2; D010750:Phosphoproteins; D014409:Tumor Necrosis Factor-alpha; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; C018315:hexon capsid protein, Adenovirus; D019041:L-Selectin; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens
keywords: Th1 cytokines; adenovirus; adoptive T-cell transfer; cytomegalovirus