Termination of the B cell lymphoma dormant state in thymectomized AKR mice.
AKR mice are highly susceptible to spontaneous T cell lymphomagenesis and thymus removal at the age of 1 to 3 mo greatly reduces its development. Twelve-mo-old AKR mice thymectomized at young age were shown previously to carry potential lymphoma cells that could be triggered to develop into B cell lymphomas (80 to 100%) after removal from their host "restrictive" environment into young histocompatible hosts. Additional attempts were made to terminate the potential lymphoma cell dormant state in 12-mo-old thymectomized AKR mice. Replenishment of some deficiencies caused by thymectomy at a young age, including a s.c. syngeneic thymus graft or a single injection of the dual tropic recombinant virus isolates DTV-71 or MCF-247 into 12-mo-old thymectomized AKR mice resulted in Ly-1+ pre-B or B cell lymphoma development in 80 to 98% of these treated mice. In vivo elimination of T cell subsets by administration of cyclosporin A or by mAb expressed on Th cells (anti-CD4) or cytotoxic T cells (anti-CD8) stimulated the progression of dormant potential lymphoma cells towards B cell lymphoma development. The most striking results were observed after administration of anti-CD8 mAb: 90 to 100% of these treated mice developed Ly-1+ B cell lymphomas within 80 days. The effect of rIL-2 on dormant PLC was also tested. Administration of rIL-2 to 12-mo-old thymectomized mice terminated tumor dormancy in 94% of the treated mice within 66 days. Tests of the resulting B lymphomas for dual tropic recombinant virus/mink cell focus-inducing virus infection indicated that the breakdown of tumor dormancy did not result from development of pathogenic class I mink cell focus-inducing viruses. These results suggest that T cell subsets and/or their products are involved in the proliferation arrest of potential lymphoma cells present in thymectomized AKR mice.
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
N
N
Haran-Ghera
A
A
Peled
B K
BK
Brightman
H
H
Fan
D000818:Animals; D015139:Blotting, Southern; D016827:CD8 Antigens / Q000502:physiology; D007376:Interleukin-2 / Q000494:pharmacology; D016393:Lymphoma, B-Cell / Q000209:etiology* / Q000235:genetics / Q000382:microbiology; D051379:Mice; D008806:Mice, Inbred AKR; D008908:Mink Cell Focus-Inducing Viruses / Q000472:pathogenicity; D012150:Polymorphism, Restriction Fragment Length; D011994:Recombinant Proteins / Q000494:pharmacology; D015183:Restriction Mapping; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013934:Thymectomy; D013950:Thymus Gland / Q000276:immunology*
D016827:CD8 Antigens; D007376:Interleukin-2; D011994:Recombinant Proteins