Adrenal participation in thymocyte death by anti-CD3 antibodies in vivo.
The deletion of CD4- and CD8-double-positive (DP) cells in the thymus after treatment with anti-CD3 antibodies has long been considered as a useful model for clonal deletion during T cell development, although it was reported that DP cell death was not observed in neonates where self-tolerance should be developing. We dealt with the cellular basis of this enigmatic phenomenon in this report. Due to the similar susceptibility to the antibody-treatment in vitro between neonatal and adult thymocytes, critical factors may be outside rather than within the thymus. Indeed, newborn thymus lobes transplanted into recipients of different ages showed an increased susceptibility to the thymo-toxicity as the age of the recipient increased. The thymo-toxicity seems to be based on the adrenal function of glucocorticoid (GC) synthesis, because administration of an inhibitor of GC synthesis significantly reduced the DP cell death by the antibody-treatment. Finally, adrenalectomy completely prevented DP cell death by anti-CD3 antibodies in adult mice. Therefore, the thymocyte death by anti-CD3 antibodies in vivo may not be due to the T cellreceptor mediated selection in the thymus.
Yoshida
Mitsuo
M
Laboratory of Immunobiology, Department of Life Science, Graduate School of Science and Technology, Niigata University, Japan.
Gotoh
Ken
K
Fujii
Masato
M
Shimada
Hiroto
H
Touma
Maki
M
Hosono
Masamichi
M
D000311:Adrenal Glands / Q000276:immunology*; D000315:Adrenalectomy; D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000276:immunology*; D000963:Antimetabolites / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D000906:Antibodies; D000963:Antimetabolites; D017252:CD3 Complex; D008797:Metyrapone