Cellular immune responses in acute leukaemia patients with severe chemotherapy-induced leucopenia; characterization of the cytokine repertoire of clonogenic T cells

Cancer Immunol Immunother. 1998 Jun;46(4):221-8. doi: 10.1007/s002620050481.

Abstract

T lymphocytes are important both for the host defence against infections and probably also as antileukaemic effector cells in patients with acute leukaemia. To investigate the T lymphocyte cytokine repertoire of clonogenic T lymphocytes, CD4+ and CD8+ T lymphocyte clones were prepared from acute leukaemia patients with chemotherapy-induced cytopenia (leucocytes <0.5x 10(9)/l). A majority of both CD4+ and CD8+ clones secreted detectable interleukin-2 (IL-2), IL-10, IL-13, granulocyte/macrophage-colony-stimulating factor and interferon gamma (IFNgamma) in response to phytohaemagglutinin + accessory cells (Epstein-Barr-virus-transformed B cell line, 80-Gy-irradiated). The CD4+ clones showed significantly higher levels of IL-10 secretion than the CD8+ clones. Decreased levels of IL-2, IL-13 and IFNgamma were observed when acute myelogenous leukaemia (AML) blasts were used instead of cells from the B cell line as accessory cells during phytohaemagglutinin activation, but the differences in IL-13 and IFNgamma levels were reversed by addition of exogenous IL-2. On the basis of these results we conclude: (i) the remaining clonogenic T lymphocytes derived from acute leukaemia patients with therapy-induced leucopenia can respond to activation with a broad cytokine response, and T-cell-derived cytokines may then contribute to cytokine responses during complicating infections in these patients; (ii) although T cells can modulate AML blast functions and mediate antileukaemic effects, the leukaemia blasts will also modulate T cell functions and alter the cytokine profile of activated T lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Clone Cells
  • Cytarabine / administration & dosage
  • Cytarabine / adverse effects
  • Cytokines / immunology*
  • Cytokines / metabolism
  • Daunorubicin / administration & dosage
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Interleukin-10 / metabolism
  • Interleukin-2 / immunology
  • Interleukin-2 / metabolism
  • Leukemia, Myeloid / blood
  • Leukemia, Myeloid / drug therapy
  • Leukemia, Myeloid / immunology*
  • Leukopenia / chemically induced*
  • Leukopenia / immunology*
  • Lymphopenia / chemically induced
  • Lymphopenia / immunology
  • Male
  • Middle Aged
  • Phytohemagglutinins / pharmacology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / blood
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology*
  • Stimulation, Chemical

Substances

  • Antineoplastic Agents
  • Cytokines
  • Interleukin-2
  • Phytohemagglutinins
  • Cytarabine
  • Interleukin-10
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Daunorubicin