Chemicals trophic for the thymus: risk for immunodeficiency and autoimmunity.
The thymus is considered as the privileged site of T-lymphocyte generation. The organ is extremely vulnerable to the toxic action of chemicals. The classical example is the "acute stress-induced involution" mediated by glucocorticoid steroid hormones from the adrenal cortex. Nowadays a number of substances have been identified that act in a differential way on the thymus. Examples presented are some organotin compounds acting on immature lymphoblasts in the outer cortex, glucocorticosteroids acting on small thymocytes in the cortex, 2,3,7,8-tetrachlorodibenzo-p-dioxin acting on epithelial cells in the cortex, and cyclosporin acting on dendritic cells and epithelium in the medulla. The mechanisms of toxicity include receptor binding (Ah, aryl hydrocarbon receptor; dioxin); the Ca(2+)-dependent activation of an endogenous endonuclease resulting in DNA fragmentation ("programmed cell death" or apoptosis; dioxin and glucocorticosteroids); and interference with cell proliferation (some organotin compounds). The consequences of toxicity can be a decrease in thymic output of newly-generated T-lymphocytes (i.e. generation of a new T-cell repertoire), or induction of autoimmune symptoms by the creation of unwanted repertoire. This latter phenomenon may be applicable to cyclosporin that under specified conditions can induce so-called syngeneic graft-vs-host disease. This survey presents a brief description of the function of the thymus and the various thymic cell populations involved. Thereafter the susceptibility to toxic insults and the mechanisms of toxicity are reviewed. Finally, the consequences of toxic action for the host defence system, and hence the health status, are considered.
Schuurman
H J
HJ
Laboratory for Pathology, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
Van Loveren
H
H
Rozing
J
J
Vos
J G
JG
D000305:Adrenal Cortex Hormones / Q000009:adverse effects / Q000633:toxicity; D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced*; D016923:Cell Death / Q000187:drug effects; D016572:Cyclosporine / Q000633:toxicity; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D009947:Organotin Compounds / Q000009:adverse effects / Q000633:toxicity; D000072317:Polychlorinated Dibenzodioxins / Q000009:adverse effects / Q000633:toxicity; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D009947:Organotin Compounds; D000072317:Polychlorinated Dibenzodioxins; D016572:Cyclosporine