Ascitic growth of a spontaneous transplantable T cell lymphoma induces thymic involution. 2. Induction of apoptosis in thymocytes.
It has been observed that the progressive ascitic growth of a transplantable T cell lymphoma of spontaneous origin, designated as Dalton's lymphoma (DL), induces inhibition of various immune responses and is associated with an involution of the thymus accompanied by a massive depletion of the cortical region and alteration in the distribution of thymocytes, with a decrease in CD4+CD8+, CD4+CD8- and CD4-CD8+ thymocytes. Morphological evaluation of thymocytes from DL-bearing mice revealed that with the progression of DL, a majority of thymocytes exhibited morphological features characteristic of apoptotic cell death, which included contracted cell bodies, condensed, uniformly circumscribed and densely stained chromatin, and membrane-bound apoptotic bodies containing one or more nuclear fragments. Quantitative and qualitative analysis of the DNA extracted from the thymocytes of DL-bearing mice revealed DNA fragmentation that increased concomitantly with the progression of DL and showed an oligonucleosomal DNA ladder pattern upon agarose gel electrophoresis, a hallmark of apoptotic cell death. Attempts to identify apoptotic factor(s) showed that the serum of DL-bearing mice contained certain soluble factor(s) that augmented the induction of apoptotis in thymocytes in a time- and dose-dependent manner. Although DL cells or their products, such as DL-cell-conditioned medium or DL-cell-free ascitic fluid, could also induce apoptosis of thymocytes in vitro, the magnitude of the same was consistently lower than that induced by the serum of DL-bearing mice. Further, elucidation of the mechanism of apoptosis induction in thymocytes with respect to the involvement of apoptosis-related genes revealed that the death pathway followed an interleukin-1 beta-converting-enzyme-dependent, Fas-mediated apoptotic cascade, with a concomitant increase in the protein products of the bax, bad, p53, fas and fasL genes and cleavage of the 23-kD N-terminal fragment of Bcl-2 that exhibited Bax-like death effector properties.
Shanker
A
A
School of Biotechnology, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
Singh
S M
SM
Sodhi
A
A
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D051033:Apoptosis Inducing Factor; D001201:Ascites / Q000473:pathology; D001202:Ascitic Fluid / Q000378:metabolism; D061945:Caspase Inhibitors; D002455:Cell Division / Q000502:physiology; D003470:Culture Media; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D053938:DNA Fragmentation; D053222:Fas Ligand Protein; D005260:Female; D005420:Flavoproteins / Q000097:blood / Q000378:metabolism; D016399:Lymphoma, T-Cell / Q000097:blood / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins / Q000097:blood / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009707:Nucleosomes / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology*
D000906:Antibodies; D051033:Apoptosis Inducing Factor; D061945:Caspase Inhibitors; D003470:Culture Media; D015853:Cysteine Proteinase Inhibitors; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D005420:Flavoproteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009707:Nucleosomes; D009842:Oligopeptides; C494830:AIFM1 protein, mouse; C096429:L 709049