T cell-dependent loss of proliferative responsiveness to colony-stimulating factor-1 by a murine epidermal-derived dendritic cell line, XS52.
We have reported previously that XS52 cells, a long-term dendritic cell (DC) line established from mouse epidermis, proliferate maximally in response to CSF-1, and that XS52 cells expanded in this manner induce brisk proliferation of HDK-1 T cells (KLH-specific Th1 clone) and 5S8 T cells (DNBS-specific Th0 clone) in the presence of Ag. Our purpose was to determine whether CSF-1-dependent mitotic potential of XS52 cells might be affected upon Ag-dependent interaction with these T cell clones. Both surface CSF-1R expression and mitotic responsiveness to CSF-1 became undetectable within 24 h after incubation with each T cell clone in the presence of relevant Ag. By contrast, incubation with T cells alone or Ag alone had minimal effect, indicating a requirement for both T cells and Ag. Exposure of fresh XS52 cells to the supernatant collected from complete XS52/HDK-1/KLH or XS52/5S8/DNBS coculture was sufficient to abrogate both CSF-1R expression and CSF-1 responsiveness. Importantly, both were restored by mAb against IFN-gamma, and both were diminished by rIFN-gamma in the absence of T cells or Ag. Thus, IFN-gamma, which was detected in relatively large amounts in the above supernatants, serves as a major mediator. rIFN-gamma reduced the number of CSF-1 binding sites on XS52 cell surface, without affecting CSF-1R mRNA expression. Thus, it appears that IFN-gamma down-regulates CSF-1R by a post-transcriptional mechanism. We interpret these results to document a novel, bi-directional signaling event in which Ag-dependent DC-T cell interaction promotes the growth of T cells, but inhibits the growth of DC.
Kitajima
T
T
Department of Dermatology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Ariizumi
K
K
Bergstresser
P R
PR
Takashima
A
A
D000818:Animals; D000941:Antigens / Q000494:pharmacology; D002455:Cell Division; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology*; D015536:Down-Regulation; D006433:Hemocyanins / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D016184:Receptors, Colony-Stimulating Factor / Q000096:biosynthesis; D015398:Signal Transduction; D012867:Skin / Q000166:cytology; D018417:Th1 Cells / Q000276:immunology*
D000941:Antigens; D012333:RNA, Messenger; D016184:Receptors, Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin