Selective abnormalities in the thymic microenvironment associated with avian scleroderma, an inherited fibrotic disease of L200 chickens.
As a prelude to deciphering the mechanisms of intrathymic T-cell maturation we produced a panel of 18 monoclonal antibodies (mAbs) against chicken thymic stromal elements. Eleven of these detected epithelial cells. They were: pan-epithelial; subcapsule and peri-vascular (pan type 1 epithelium); subcapsular, perivascular and medulla; medulla; or cortex. Of particular interest were the sub-specificities within these regions, especially the subcapsular region. Four mAbs stained both epithelial and non-epithelial cells in discrete regions. In addition, three mAbs recognized only non-epithelial cells. One identified macrophages scattered throughout the thymus, another the connective tissue and another the medullary vascular endothelium. These reagents have provided an extensive profile of the thymic stromal architecture and revealed that these cells are equally as complex as the T cells whose differentiation they induce and regulate. While the mAbs provide a valuable means for studying the mechanisms of normal thymopoiesis, their clinical significance is unknown. UCD line 200 chickens develop an autoimmune disease manifest by dermal and internal organ fibrosis, T cell infiltrates of skin and other affected organs and production of multiple autoantibodies. We have used our panel of mAbs to evaluate the thymic microenvironment in these autoimmunity-prone chickens. A comparative analysis with control chickens revealed striking deficiencies in the L200 subcapsular regions coupled with excessive expression of MHC class II antigens, particularly in the cortex. We hypothesize that these abnormalities induce altered T-cell differentiation, thereby predisposing the L200 chickens to autoimmune disease.
Boyd
R L
RL
Department of Pathology and Immunology, Monash University, Prahran, Australia.
Wilson
T J
TJ
Van De Water
J
J
Haapanen
L A
LA
Gershwin
M E
ME
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D002454:Cell Differentiation; D002645:Chickens / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D004848:Epithelium / Q000276:immunology / Q000473:pathology; D005455:Fluorescent Antibody Technique; D012595:Scleroderma, Systemic / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology*; D013951:Thymus Hormones / Q000172:deficiency
D000911:Antibodies, Monoclonal; D013951:Thymus Hormones