Th1 and Th2 clones differ in their response to a tolerogenic signal.
Th1 and Th2 clones specific for human gamma globulin (HGG) were compared and shown to differ in terms of the effects of tolerance induction on Ag-induced proliferation and helper activity. In developing a method to induce tolerance, splenic APC that had been pulsed with HGG and then fixed with 0.15% paraformaldehyde (HGG-FAPC) were used as a means to present Ag to the Th clones in the absence of costimulatory signals. Both Th1 and Th2 clones recognized HGG-FAPC as evidenced by their ability to proliferate to HGG-FAPC. Unlike Th2, Th1 proliferated to HGG-FAPC only in the presence of T cell-depleted allogeneic spleen cells as a source of accessory cell signals. The inability of Th1 cells to proliferate in the absence of costimulatory signals was due to Ag-specific inactivation: Th1 clones preincubated with HGG-FAPC were unable to proliferate when recultured with HGG and irradiated APC. In contrast to Th1 clones, Th2 clones showed no decrease in their Ag-induced proliferative capacity after exposure to any concentration of HGG-FAPC. However, when examined by using a second assay system, that of providing help for anti-HGG antibody production by primed B cells, Th2 preincubated with HGG-FAPC were markedly inhibited (up to 90%) in their ability to provide help. Preincubation with HGG-FAPC also inhibited the helper activity of the one Th1 clone that was found to induce a significant secondary antibody response. Taken together, the results suggest that exposure of Th1 to tolerogen in the form of HGG-pulsed fixed APC inactivates Th1 proliferative capacity, and possibly Th1 helper activity as well. Exposure of Th2 cells to a tolerogen suppresses the mechanism by which the Th2 cells provide Ag-induced B cell help, but does not inhibit the mechanism by which they proliferate to HGG. Furthermore, the results define a model that incorporates Ag processing as well as Ag presentation in the induction of tolerance in vitro.
Research Institute of Scripps Clinic, Department of Immunology, La Jolla CA 92037.
K M
KM
Gilbert
K D
KD
Hoang
W O
WO
Weigle
D000818:Animals; D000917:Antibody Formation; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D016827:CD8 Antigens; D002999:Clone Cells; D005557:Formaldehyde / Q000494:pharmacology; D007108:Immune Tolerance; D007156:Immunologic Memory; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011108:Polymers / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D005719:gamma-Globulins / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D011108:Polymers; D005719:gamma-Globulins; D005557:Formaldehyde; C003043:paraform