T cell-replacing activity of C8-derivatized guanine ribonucleosides.
The capacity of the C8-substituted guanine ribonucleosides to provide T cell-like signals to cultures of splenic B cells was evaluated. We showed previously that these low m.w. nucleoside derivatives traverse the cell membrane and induce their effects from an intracellular location. The current studies clearly demonstrate that 8 mercaptoguanosine (8MGuo), when added to cultures of B cells and macrophages in the presence of antigen, is capable of supplying a "second signal" for B cells, enabling them to generate high numbers of specific plaque-forming cells against the immunizing antigen. This effect is duplicated in cultures of spleen cells from congenitally athymic mice. Inhibition of interleukin 2 (IL 2) generation by cyclosporin A, such that the antibody response of normal spleen cells is entirely abrogated, has minimal effects on the T cell-replacing activity of 8MGuo. Additivity studies with MLC supernatants as well as kinetic analyses with IL 2-associated lymphokines substantiate that these factors act by a mechanism distinct from that of 8MGuo and 8BrGuo. These observations establish these nucleoside activators as exciting new probes for T helper cell activity and an effective non-T cell source of T cell-like signals.
D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology; D003524:Cyclosporins / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology*; D006151:Guanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006462:Hemolytic Plaque Technique; D007376:Interleukin-2 / Q000502:physiology; D015848:Interleukin-5; D007700:Kinetics; D007959:Lymphocyte Culture Test, Mixed; D008222:Lymphokines / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008819:Mice, Nude; D013601:T-Lymphocytes / Q000276:immunology
D003524:Cyclosporins; D006146:Guanidines; D007376:Interleukin-2; D015848:Interleukin-5; D008222:Lymphokines; D006151:Guanosine; C035169:8-bromoguanosine; C100078:2-mercaptoethylguanidine