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Journal of Histochemistry and Cytochemistry, Vol. 45, 129-142, Copyright © 1997 by The Histochemical Society, Inc.

ARTICLE

Thymic Overexpression of CD40 Ligand Disrupts Normal Thymic Epithelial Organization

Robert J. Dunna, Carrie J. Luedeckera, Harald S. Haugenc, Christopher H. Cleggc, and Andrew G. Farra,b
a Department of Biological Structure, University of Washington, Seattle, Washington
b Department of Immunology, University of Washington, Seattle, Washington
c Bristol Myers/Squibb Pharmaceutical Research Institute, Seattle, Washington

Correspondence to: Andrew G. Farr, Dept. of Biological Structure, Box 357420, U. of Washington, Seattle, WA 98195-7420.

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. (J Histochem Cytochem 45:129-141, 1996)

Key Words: Thymic epithelium, CD40-L, CD40, gp39


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