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Laboratories of Cellular Physiology and Immunology and
Molecular Biology and Biochemistry, Rockefeller University, New York, NY 10021
These studies were performed to establish whether functional
receptors for calcitonin gene-related peptide (CGRP) are present on
human dendritic cells (DCs) and to investigate potential
immunomodulatory effects of CGRP on DCs other than Langerhans cells.
Reverse transcriptase-PCR revealed expression of mRNA for a type 1 CGRP
receptor by mature and immature blood-derived DCs. Sequence analysis
confirmed the identity of the type 1 CGRP receptor (CGRP-R1). Addition
of CGRP (10-7 M) to mature and immature DCs resulted in
mobilization of intracellular calcium. Treatment of immature DCs with
CGRP (10-7 M), before and after maturation in
monocyte-conditioned medium, resulted in decreased cell surface
expression of HLA-DR MHC class II and the costimulatory molecule, CD86.
Treatment of immature DCs with CGRP (10-7 M) also resulted
in decreased expression of CD86, but expression of HLA-DR was
unchanged. When CGRP-treated mature DCs were used to stimulate
allogeneic T cells, proliferative responses were dampened (
50%),
especially at low DC:T cell ratios (1:360). This effect was not
observed with CGRP-treated, immature DCs. In contrast, CGRP-treated
mature or immature DCs were no less efficient than untreated DCs in
driving syngeneic T cell-proliferative responses to staphylococcal
enterotoxin B. We conclude that mature and immature DCs express type 1
CGRP receptors and that signaling through these receptors may dampen
mature DC-driven T cell proliferation most likely via down-regulation
of CD86 and HLA-DR.
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