The Journal of Immunology, Vol 155, Issue 11 5190-5197, Copyright © 1995 by American Association of Immunologists

ARTICLES

T cell-dependent loss of proliferative responsiveness to colony- stimulating factor-1 by a murine epidermal-derived dendritic cell line, XS52

T Kitajima, K Ariizumi, PR Bergstresser and A Takashima
Department of Dermatology, University of Texas Southwestern Medical Center, Dallas 75235, USA.

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.

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