The allogeneic effect: the mechanism of allosuppression by Lyt-1, Ia- T cells.
The kinetics of allohelp mediated by diffusable factors revealed that help by nonirradiated T cells (TOR) peaked at 48 to 72 hr, followed by a sharp decline if the T cells remained in the cultures. The temporal decrease in help after 72 hr was not mediated by suppressor lymphokines because mixtures of early (24 to 48 hr) and late (120-hr) allogeneic supernatants enhanced help synergistically. Lyt-1, Ia- T cells mediated the temporal decline in help and suppressed allogeneic B cell activation in co-cultures, and this "down-regulatory" activity (allosuppression) was radiosensitive. Help by irradiated T cells (T1000R) increased gradually until it plateaued between 96 and 120 hr. The helper activities of the allogeneic supernatants were directly proportional to their T cell growth factor (TCGF) activities. In addition, their kinetics were identical, and the removal of TCGF from 48-hr allogeneic supernatants by adsorption with TCGF-dependent HT-2 cells depleted both helper and TCGF activities. Help was restored to depleted 48-hr and 120-hr allogeneic supernatants by preparations of TCGF obtained from concanavalin A (Con A)-stimulated FS6-14.13 hybridoma cells that were adsorbed with lipopolysaccharide (LPS)-activated B cells or normal spleen cells (NS), but not with HT-2 cells. These results indicate that allohelp is dependent on TCGF. Moreover, help was dependent on at least one factor in addition to TCGF, because a high level of synergy occurred between TCGF and the "help-deficient" 120-hr allogeneic supernatant. In conclusion, the mechanism whereby Lyt-1, Ia- T cells regulated B cell activation with positive and negative allogeneic effects was through the production and subsequent exhaustion of TCGF, respectively. The production of TCGF and help was radioresistant, but exhaustion of TCGF and suppression was radiosensitive.
D000818:Animals; D000950:Antigens, Ly / Q000235:genetics*; D002469:Cell Separation; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D007376:Interleukin-2 / Q000378:metabolism / Q000502:physiology; D007700:Kinetics; D007959:Lymphocyte Culture Test, Mixed; D008222:Lymphokines / Q000096:biosynthesis / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D013491:Suppressor Factors, Immunologic; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000950:Antigens, Ly; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D008222:Lymphokines; D013491:Suppressor Factors, Immunologic; C022780:allogenic effect factor