Interleukin 1 production during accessory cell-dependent mitogenesis of T lymphocytes.
We have studied the control and significance of IL-1 production in human leukocyte cultures during accessory cell-dependent, T lymphocyte mitogenesis using sensitive bioassays and immunolabeling techniques. In primary antigen-dependent systems like the MLR, IL-1 production was not detected in accessory cells (monocytes, dendritic cells) or T cells, suggesting that it is not an early product in these responses. However, monocytes could be induced to make IL-1 after interacting with sensitized antigen-specific T cells. Both alloreactive T cell clones or freshly prepared lymphoblasts induced IL-1 provided the monocytes carried the HLA-DR antigens to which the T cells were initially sensitized. Even in these circumstances, dendritic cells and B cells failed to make IL-1. The mechanism whereby activated T cells induce IL-1 in monocytes was explored. Supernatants from cocultures of monocytes and T cells or several recombinant cytokines induced little or no IL-1. A more potent antigen independent pathway of IL-1 induction was identified. IL-1 could be induced in third-party HLA-DR nonspecific monocytes in cocultures of alloreactive T cell clones or blasts and HLA-DR-specific dendritic cells. The induction was factor independent since dendritic cells and T blasts placed in a chamber separate from third-party monocytes by a semipermeable membrane did not induce monocyte IL-1. These results suggest that a cell contact mechanism rather than an IL-1-inducing factor leads to IL-1 production. The role of IL-1 in T cell proliferation was tested with a polyclonal anti-IL-1 antibody. The antibody failed to block the proliferation of primary T cells, or alloreactive T cell clones and blasts stimulated with HLA-specific monocytes or dendritic cells, even though IL-1 in the medium was neutralized.
Bhardwaj
N
N
Rockefeller University, New York, New York 10021.
Lau
L L
LL
Friedman
S M
SM
Crow
M K
MK
Steinman
R M
RM
D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003208:Concanavalin A / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007118:Immunoassay; D007375:Interleukin-1 / Q000096:biosynthesis*; D007700:Kinetics; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D006684:HLA-DR Antigens; D007375:Interleukin-1; D008070:Lipopolysaccharides; D003208:Concanavalin A