Delayed kinetics of T lymphocyte anergy and deletion in lpr mice.
The Fas/APO-1 (Fas) antigen is a cell surface protein that mediates apoptosis and belongs to the tumor necrosis factor receptor family. The lymphoproliferative (lpr) anomaly in mice results from a retroviral disruption within the fas gene. Mice that are homozygous for the lpr mutation accumulate large numbers of T lymphocytes and exhibit an autoimmune syndrome resembling systemic lupus erythematosus. A possible explanation for this process is that in the absence of Fas antigen, lpr T cells may be resistant to normal peripheral deletional signals. The bacterial superantigen staphylococcal enterotoxin B (SEB) rapidly induces anergy and deletion by apoptosis of reactive T lymphocytes in normal mice. Administration of SEB to adult lpr mice results in the delayed induction of both unresponsiveness and deletion of V beta 8+ lymph node cells. This is not due merely to an increased thymic output in lpr mice; the delayed induction of tolerance and elimination of reactive lpr T cells by superantigens are intrinsic properties of the cells. The progressive lymphadenopathy in lpr mice may reflect a process of lymphoaccumulation rather than lymphoproliferation. A delay in tolerance induction and elimination of self-reactive T cells could have profound influence on the autoimmune diathesis of lpr mice.
Mixter
P F
PF
Department of Medicine, University of Vermont College of Medicine, Burlington 05405-0068.
Russell
J Q
JQ
Budd
R C
RC
D000367:Age Factors; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017635:Clonal Anergy; D017637:Clonal Deletion; D004768:Enterotoxins / Q000494:pharmacology*; D007108:Immune Tolerance; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013934:Thymectomy; D013950:Thymus Gland / Q000502:physiology; D019014:fas Receptor
D000954:Antigens, Surface; D004768:Enterotoxins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019014:fas Receptor; C031818:enterotoxin B, staphylococcal