Evidence for clonal deletion and clonal anergy after intrathymic antigen injection in a transplantation model.
Intrathymic (IT) antigen injection has been shown to induce antigen-specific systemic tolerance in the rodent. To delineate the mechanisms responsible for the induction of tolerance, we used the 2C line of T cell receptor transgenic mice. The majority of T cells in 2C mice express an antigen receptor specific for the major histocompatibility complex class I alloantigen Ld and can be identified with the clonotypic monoclonal antibody 1B2. IT injection of lymphoid cells expressing Ld was found to induce a significant prolongation in BALB/c skin allograft survival. The allograft prolongation was associated with a marked reduction in the number of developing 1B2+ thymocytes (clonal deletion), which occurred primarily at the CD4+ CD8+ stage of thymocyte development, as well as a reduction in the number of mature CD8+ 1B2+ 2C T cells in peripheral lymphoid tissue. In addition, CD8+ 1B2+ 2C T cells that survive deletion have decreased CD8 expression levels and a significantly reduced in vitro proliferative response to specific alloantigen (clonal anergy). Exogenous recombinant interleukin 2 restores the capacity of 2C T cells to respond in vitro to alloantigen. Experiments involving separation of cells by fluorescence-activated cell sorter indicate that there is a precise correlation between the reduction in CD8 expression and anergy induction. Collectively, these data indicate that IT antigen injection can induce antigen-specific systemic tolerance by both clonal deletion and clonal anergy.
Gillanders
W E
WE
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Arima
T
T
Tu
F
F
Hansen
T H
TH
Flye
M W
MW
D019264:Adoptive Transfer; D000818:Animals; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D017635:Clonal Anergy; D017637:Clonal Deletion / Q000235:genetics; D000939:Epitopes / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects; D007272:Injections, Intralymphatic; D007274:Injections, Intraperitoneal; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016377:Organ Transplantation / Q000502:physiology*; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology; D013154:Spleen / Q000166:cytology; D013950:Thymus Gland; D014181:Transplantation Immunology
D000961:Antilymphocyte Serum; D000939:Epitopes; D016693:Receptors, Antigen, T-Cell, alpha-beta