Tolerance induction of allo-class II H-2 antigen-reactive L3T4+ helper T cells and prolonged survival of the corresponding class II H-2-disparate skin graft.
The present study investigates the effects of i.v. presensitization with class II H-2-disparate allogeneic cells on various L3T4+ T cell functions including the capability of rejecting the corresponding allogeneic skin graft. C57BL/6 (B6) mice were i.v. presensitized with class II H-2 disparate B6-C-H-2bm12 (bm12) spleen cells. Such presensitization did not affect the bm12-specific L3T4+ T cell-mediated proliferative and interleukin 2 (IL-2)-producing capacities. A single cell suspension of (B6 x bm12)F1 spleen cells was depleted of APC by two round-passages over Sephadex G-10 columns. This APC-depleted fraction of (B6 x bm12)F1 cells failed to stimulate B6 responding cells in mixed lymphocyte reactions (MLR). The addition of recombinant IL-1 to the MLR restored anti-bm12 MLR responses, indicating that APC-depleted (B6 x bm12)F1 cells bear bm12 alloantigens but are unable to stimulate B6 anti-bm12 L3T4+ T cells. A single i.v. administration of APC-depleted (B6 x bm12)F1 cells into B6 mice resulted in almost complete abrogation of the capacity of recipient B6 lymphoid cells to give anti-bm12 MLR and IL2 production. This suppression was bm12 alloantigen-specific and attributed to the elimination or functional impairment of anti-bm12 T cell clones rather than the induction of suppressor cells. The tolerance was also observed in graft-rejection responses. The strikingly prolonged survival of bm12 skin grafts was produced when grafts were implanted into B6 mice which had been presensitized with APC-depleted, but not with untreated (B6 x bm12)F1 spleen cells. These results indicate that allo-class II H-2 antigen-reactive L3T4+ T cells are rendered tolerant by i.v. presensitization with APC-depleted fraction of the corresponding allogeneic cells.
Hori
S
S
Biomedical Research Center, Osaka University Medical School, Japan.
Sato
S
S
Kitagawa
S
S
Azuma
T
T
Kokudo
S
S
Hamaoka
T
T
Fujiwara
H
H
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte; D005260:Female; D006085:Graft Survival; D006183:H-2 Antigens / Q000235:genetics* / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D007108:Immune Tolerance; D007116:Immunization, Passive; D007275:Injections, Intravenous; D007700:Kinetics; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010641:Phenotype; D016038:Skin Transplantation; D013045:Species Specificity; D013154:Spleen / Q000276:immunology / Q000637:transplantation; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II