title: Decreased functional T lymphocyte-mediated cytokine responses in patients with chemotherapy-induced neutropenia.
abstract: OBJECTIVE
  The degree of immunosuppression in patients with haematological malignancies treated with chemotherapy is routinely measured as number of circulating cells (preferable neutrophils) in peripheral blood. A parallel decline in the number of T cells is expected, but a possible alteration in their functionality has been less well explored. The ability of T cells to secrete more than one cytokine simultaneously is known to indicate protective immunity. The aim of this study was to determine whether the function of circulating T cells is altered in patients with chemotherapy-induced neutropenia.
  
  
  METHODS
  In this cross-sectional study, we used the FluoroSpot assay to investigate the proportion of T cells secreting either interferon-γ or interleukin-2, or both cytokines simultaneously, after anti-CD3 stimulation. Peripheral blood mononuclear cells from 53 adult patients with chemotherapy-induced neutropenia and 20 healthy individuals were investigated.
  
  
  RESULTS
  There were significantly fewer T cells secreting interferon-γ in patients with neutropenia compared with healthy control subjects (P = 0.02), but the difference was greatest for dual cytokine-secreting T cells (P = 0.001). Furthermore, the amount of secreted cytokine per T cell appeared to be reduced in patients, compared with control subjects.
  
  
  CONCLUSIONS
  Our results suggest that the functionality of T cells is altered in patients with haematological malignancies with chemotherapy-induced neutropenia. In parallel with a decline in T cell count, this may further increase the risk of severe infections.
authors.affiliation: Department of Medicine, Solna, Infectious Diseases Unit, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Öhrmalm
authors.forename: C
authors.initials: C
authors.lastname: Smedman
authors.forename: M
authors.initials: M
authors.lastname: Wong
authors.forename: K
authors.initials: K
authors.lastname: Broliden
authors.forename: T
authors.initials: T
authors.lastname: Tolfvenstam
authors.forename: O
authors.initials: O
authors.lastname: Norbeck
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000378:metabolism*; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology; D009503:Neutropenia / Q000139:chemically induced* / Q000276:immunology; D013548:Sweden; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016207:Cytokines; D007376:Interleukin-2; D007371:Interferon-gamma
keywords: T cell; cytokines; haematology; neutropenia