Thymic overexpression of CD40 ligand disrupts normal thymic epithelial organization.
We characterized the distribution of CD40 and CD40 ligand (CD40-L) in the adult and developing murine thymus. Before birth, CD40 was almost exclusively localized to scattered foci of medullary cells. By birth there was a dramatic upregulation of CD40 expression by cortical epithelial cells, which was accompanied by a consolidation of medullary epithelial foci. CD40-L+ thymocytes displayed a medullary location. Analysis of mice deficient in CD40-L expression indicated that CD40-L/CD40 interactions were not required for development of the medullary compartment. Overexpression of CD40-L targeted to thymocytes altered thymic architecture, as reflected by a dramatic loss of cortical epithelial cells, expansion of the medullary compartment, and extensive infiltration of the capsule with a mixture of CD3+ cells, B-cells, and macrophages/dendritic cells. Reconstitution of lethally irradiated normal mice with lck CD40-L bone marrow cells also resulted in loss of cortical epithelium and expansion of the medullary compartment. Disruption of the normal pattern of thymic architecture and epithelial differentiation as a consequence of increased intrathymic levels of CD40-L expression points to a role for CD40-L/CD40 interactions in the normal pattern of epithelial compartmentalization/differentiation within the thymic environment.
Dunn
R J
RJ
Department of Biological Structure, University of Washington, Seattle, USA.
Luedecker
C J
CJ
Haugen
H S
HS
Clegg
C H
CH
Farr
A G
AG
D000818:Animals; D019013:CD40 Antigens / Q000032:analysis / Q000378:metabolism*; D023201:CD40 Ligand; D002454:Cell Differentiation; D002478:Cells, Cultured; D004847:Epithelial Cells; D005260:Female; D018390:Gene Targeting; D007124:Immunoenzyme Techniques; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016253:Microscopy, Immunoelectron; D017154:Stromal Cells / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000196:embryology / Q000254:growth & development* / Q000276:immunology / Q000378:metabolism
D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D023201:CD40 Ligand