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Blood, Vol. 94 No. 6 (September 15), 1999:
pp. 1890-1898
Macrophage-Derived Chemokine Is Localized to Thymic Medullary
Epithelial Cells and Is a Chemoattractant for CD3+,
CD4+, CD8low Thymocytes
David Chantry,
Paola Romagnani,
Carol J. Raport,
Christi L. Wood,
Angela Epp,
Sergio Romagnani, and
Patrick W. Gray
From ICOS Corp, Bothell, WA; and the Department of Clinical
Physiopathology, Endocrinology Unit, and the Institute of Internal
Medicine and Immunoallergy, University of Florence, Italy.
Macrophage-derived chemokine (MDC) is a recently identified CC
chemokine that is a potent chemoattractant for dendritic cells, natural
killer (NK) cells, and the Th2 subset of peripheral blood T cells. In
normal tissues, MDC mRNA is expressed principally in the thymus.
Immunohistochemical analysis performed on 5 human postnatal thymuses
showed high MDC immunoreactivity, which was selectively localized to
epithelial cells within the medulla. To examine the effects of MDC on
immature T cells, we have identified cDNA clones for mouse and rat MDC.
Expression of MDC in murine tissues is also highly restricted, with
significant levels of mRNA found only in the thymus. Thymocytes express
high-affinity binding sites for MDC (kd = 0.7 nmol/L),
and, in vitro, MDC is a chemoattractant for these cells. MDC-responsive
murine thymocytes express mRNA for CCR4, a recently identified receptor
for MDC. Phenotypic analysis of MDC-responsive cells shows that they
are enriched for a subset of double-positive cells that express high levels of CD3 and CD4 and that have reduced levels of CD8. This subset
of MDC-responsive cells is consistent with the observed expression of
MDC within the medulla, because more mature cells are found there. MDC
may therefore play a role in the migration of T-cell subsets during
development within the thymus.
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