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Macrophage factors which enhance the mixed leukocyte reaction initiated by dendritic cells
1Department of Zoology, Faculty of Science, Kyoto University, Japan.
Abstract:
Stimulator cells for the allogeneic MLR are dendritic cells but not macrophages (M phi). M phi, however, enhance the MLR initiated by relatively low doses of dendritic cells. The present report demonstrates that the enhancement of the MLR is mediated by two factors produced by M phi. One is IL-1, inasmuch as it has a Mr approximately 15 kDa, and both partially purified IL-1 and rIL-1 also enhance the MLR. The other has been identified as granulocyte-macrophage (GM)-CSF. It had a Mr approximately 25 kDa, and is reproduced by rGM-CSF. Moreover, the MLR-enhancing activity of both the 25-kDa molecule and rGM-CSF have been neutralized by anti-GM-CSF antiserum. Both IL-1 and GM-CSF have autonomous enhancing activity, but they collaborate with each other in enhancing the MLR. Both factors act on DC to augment their stimulatory activity for allogeneic T lymphocytes.
Insights
Macrophages enhance the mixed lymphocyte reaction (MLR) by producing two key factors: interleukin-1 (IL-1) and granulocyte-macrophage colony-stimulating factor (GM-CSF). These factors act on dendritic cells (DCs) to boost their stimulatory capacity for allogeneic T lymphocytes.
Area of Science:
- Immunology
- Cell Biology
Background:
- Dendritic cells (DCs) are primary stimulator cells in the allogeneic mixed lymphocyte reaction (MLR).
- Macrophages (M phi) do not typically initiate the MLR but can enhance it when used with low doses of DCs.
Purpose of the Study:
- To identify the factors produced by macrophages that enhance the MLR.
- To elucidate the mechanism by which these factors augment DC stimulatory capacity.
Main Methods:
- Macrophage-conditioned media were analyzed for MLR-enhancing activity.
- Purified or recombinant forms of candidate factors (IL-1, GM-CSF) were tested for their ability to enhance the MLR.
- Neutralization assays using anti-GM-CSF antiserum were performed.
Main Results:
- Two M phi-derived factors were identified: interleukin-1 (IL-1, ~15 kDa) and granulocyte-macrophage colony-stimulating factor (GM-CSF, ~25 kDa).
- Both partially purified IL-1 and recombinant IL-1 (rIL-1) enhanced the MLR.
- Recombinant GM-CSF (rGM-CSF) also enhanced the MLR, and this activity was neutralized by anti-GM-CSF antiserum.
- Both IL-1 and GM-CSF demonstrated independent enhancing activity and synergistic collaboration.
Conclusions:
- Macrophages enhance the allogeneic MLR through the secretion of IL-1 and GM-CSF.
- These cytokines act on dendritic cells, augmenting their ability to stimulate allogeneic T lymphocytes.
- IL-1 and GM-CSF collaborate to enhance DC-mediated T cell activation in the MLR.