Paracrine regulation of B-cell growth in hairy cell leukemia.
There is evidence that the growth of malignant B lymphocytes e.g. hairy cells is regulated by cytokines. Several investigators suggested that the stimulating cytokines are produced by the malignant B cells indicating an autocrine growth regulation. Here we demonstrate that T lymphocyte clones produce soluble mediators which stimulate the growth of malignant B lymphocytes. The incidence of the growth stimulating T cell clones derived from peripheral blood is identical in patients with hairy cell leukemia (HCL) and healthy controls. About 50% of the clones stimulate the growth of hairy cells, but not the growth of purified B-lymphocytes of healthy donors. The stimulating activity of a single clone varies when tested on different hairy cells. Interferon alfa but not antibodies against tumor necrosis factor alfa or interleukin-2 inhibit completely the growth stimulating activity. We propose that interferon alpha inhibits the production of soluble mediators produced by normal T-cells. Our results indicate that a paracrine growth regulation has to be considered in addition to the postulated autocrine loop in the growth regulation of malignant B cells.
Porzsolt
F
F
Department of Medicine III (Hematology and Oncology), University of Ulm, Germany.
Schmid
M
M
Staib
G
G
Schrezenmeier
H
H
D001402:B-Lymphocytes / Q000166:cytology*; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002999:Clone Cells; D003470:Culture Media; D006133:Growth Substances / Q000096:biosynthesis / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D007943:Leukemia, Hairy Cell / Q000097:blood* / Q000473:pathology*; D008969:Molecular Sequence Data; D013268:Stimulation, Chemical; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology
D003470:Culture Media; D006133:Growth Substances; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha