Stromal-derived factor 1 expression in the human thymus.
Stromal-derived factor-1 (SDF-1), the only known ligand for the chemokine receptor CXCR4, is broadly expressed in cells of both the immune and central nervous systems, and it can induce the migration of resting leukocytes and hemopoietic progenitors. SDF-1 mRNA was previously detected in human thymus-derived stromal cells, but its role in thymopoiesis was unknown. Here we show that SDF-1 is expressed in medullar epithelial cells forming Hassall's corpuscles (HC). In search of the cell type that may be attracted by SDF-1(+) cells in the medulla, we determined that dendritic cells (DC) could be found in situ in close proximity to SDF-1(+) epithelial cells in HC. In HIV-1-infected SCID-hu thymuses, DC contained apoptotic cells and were located within enlarged HC. It was further demonstrated that uptake of apoptotic thymocytes by immature DC induced an increase in CXCR4 expression and SDF-1-mediated chemotaxis. Our data suggest a role for SDF-1 in the elimination of apoptotic thymocytes.
Zaitseva
Marina
M
Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, and Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. zaitseva@cber.fda.gov
Kawamura
Tatsuyoshi
T
Loomis
Rebecca
R
Goldstein
Harris
H
Blauvelt
Andrew
A
Golding
Hana
H
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics; D002675:Child, Preschool; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000473:pathology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D051379:Mice; D016513:Mice, SCID; D010587:Phagocytosis / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000502:physiology; D017154:Stromal Cells / Q000276:immunology* / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D012333:RNA, Messenger; D019718:Receptors, CXCR4