Cellular immune responses in acute leukaemia patients with severe chemotherapy-induced leucopenia; characterization of the cytokine repertoire of clonogenic T cells.
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.
Bruserud
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Medical Department, Haukeland Hospital, Bergen, Norway.
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002999:Clone Cells; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D003630:Daunorubicin / Q000008:administration & dosage; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D007970:Leukopenia / Q000139:chemically induced* / Q000276:immunology*; D008231:Lymphopenia / Q000139:chemically induced / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D013268:Stimulation, Chemical
D000970:Antineoplastic Agents; D016207:Cytokines; D007376:Interleukin-2; D010835:Phytohemagglutinins; D003561:Cytarabine; D016753:Interleukin-10; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003630:Daunorubicin