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Effect of granulocyte-macrophage colony-stimulating factor on
lymphokine-activated killer cell induction
AM Stewart-Akers, JS Cairns, DJ Tweardy and SA McCarthy
Department of Molecular Genetics and Biochemistry, University of
Pittsburgh, PA 15213.
The treatment of cancer with lymphokine-activated killer (LAK) cells in
conjunction with high-dose interleukin-2 (IL-2) has been limited by the
toxicity of IL-2 and the narrow range of tumors that respond to therapy.
Cytokines that are capable of augmenting lower doses of IL-2 are,
therefore, a major focus of research. We report here that
granulocyte-macrophage colony-stimulating factor (GM-CSF) can augment
low-dose IL-2 LAK induction from murine splenocytes. Anti-tumor necrosis
factor alpha (anti-TNF alpha) or anti-interferon gamma (anti- IFN gamma)
monoclonal antibodies did not inhibit (IL-2 + GM-CSF)- induced LAK
generation, indicating that GM-CSF augmentation does not require TNF alpha
or IFN gamma activity. Depletion of natural killer cells before culture did
not inhibit low-dose IL-2-induced LAK generation or the ability of GM-CSF
to augment LAK generation. In contrast, depletion of both CD4+ and CD8+ T
cells before culture inhibited the generation of LAK activity. However,
depletion of only CD4+ T cells, or only CD8+ T cells, did not inhibit the
generation of IL-2 or (IL-2 + GM-CSF) LAK activity. These results suggest
that LAK precursors are present in both the CD4+ and CD8+ T-cell
populations and suggest that the addition of GM-CSF to low-dose IL-2 may
result in the generation of T-derived LAK cells.
Volume 81,
Issue 10,
pp. 2671-2678,
05/15/1993
Copyright © 1993 by The American Society of Hematology

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