Macrophage-derived chemokine and EBI1-ligand chemokine attract human thymocytes in different stage of development and are produced by distinct subsets of medullary epithelial cells: Possible implications for negative selection

The chemoattractant activity of macrophage-derived chemokine (MDC), EBI1-li gand chemokine (ELC), and secondary lymphoid tissue chemokine (SLC) on huma n thymocytes was analyzed. Both ELC and SLC caused the accumulation of CD4( +)CD8(-) or CD4(-)CD8(+) CD45RA(+) thymocytes showing high CD3 expression. By contrast, a remarkable proportion of MDC-responsive thymocytes were CD4( +)CD8(+) cells exhibiting reduced levels of CD8 or CD4(+)CD8(-) cells showi ng CD3 and CD45RO, but not CD45RA. MDC-responsive thymocyte suspensions wer e enriched in cells expressing the MDC receptor, CCR4, selectively localize d to the medulla, and in CD30(+) cells, whereas ELC-responsive thymocytes n ever expressed CD30, Reactivity to both MDC and ELC was localized to cells of the medullary areas, but never in the cortex, Double immunostaining show ed no reactivity for either MDC or ELC by T cells, macrophages, or mature d endritic cells, whereas many medullary epithelial cells were reactive to MD C or ELC, However, MDC reactivity was consistently localized to the outer w all of Hassal's corpuscles, whereas ELC reactivity was often found in cells surrounding medullary vessels, but not in Hassal's corpuscles. Moreover, w hile most MDC-producing cells also stained positive for CD30L, this molecul e was never found on ELC-producing cells. We suggest therefore that CD30L-e xpressing MDC-producing medullary epithelial cells attract CCR4-expressing thymocytes, thus favoring the CD30/CD30L interaction, and therefore the apo ptosis, of cells that are induced to express CD30 by autoantigen activation . By contrast, ELC production by CD30L-lacking medullary epithelial cells m ay induce the migration into periphery of mature thymocytes that have survi ved the process of negative selection.