Regulation of anti-hapten antibody responses in vivo: memory, carrier-specific Lyt-2+ T cells can terminate antibody production without altering the peak of response.
By using the classical hapten-carrier antigenic system (dinitrophenyl-keyhole limpet hemocyanin) (DNP-KLH), and positive immunoselective techniques for purification of lymphocyte subsets, we studied the kinetics and role of KLH-primed T cells in the termination of a secondary in vivo plaque-forming cell (PFC) response against DNP in the mouse. Separation of T cells by Lyt-2 phenotype and recombination of T cell subsets demonstrated that a single injection of KLH in complete Freund's adjuvant (CFA) concomitantly generated both helper and suppressor T cells in the spleens of primed mice. When these KLH-primed, purified T cells were transferred into irradiated recipients along with DNP-primed, purified B cells and DNP-KLH, helper activity was demonstrable first, with the early production of a high anti-DNP PFC response. Suppression of the PFC response was observed only after the response had fully developed; the PFC response was then "terminated" within a few days. Helper activity was obtained with the carrier-primed Lyt-2- T cell population, whereas suppression required the addition of Lyt-2+ T cells. Both activities were generated over a wide dose range, were specific for the priming antigen KLH, and could be detected as early as 8 days or as late as 9 mo after a single priming injection of KLH. Lyt-2+ T cells from unprimed donors or from animals primed with a different carrier did not have the capacity to terminate the response when added with the primed Lyt-2- helper T cells. Thus, we have now demonstrated the existence of carrier-specific, long-lived, "memory" suppressor T cells, which are initially generated in parallel with specific helper T cells. Whereas these memory suppressor T cells do not inhibit the induction of a secondary antibody response, they can effectively terminate it once it has developed, and may therefore account for the normal termination of antibody responses.
D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D000950:Antigens, Ly / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology*; D004140:Dinitrophenols; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes; D005260:Female; D006241:Haptens / Q000276:immunology*; D006433:Hemocyanins; D006462:Hemolytic Plaque Technique; D007156:Immunologic Memory; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000276:immunology; D013234:Stem Cells / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000941:Antigens; D000950:Antigens, Ly; D002352:Carrier Proteins; D004140:Dinitrophenols; D000939:Epitopes; D006241:Haptens; C034638:dinitrophenyl-bovine serum albumin; D012710:Serum Albumin, Bovine; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin