Pertussis toxin prevents the induction of peripheral T cell anergy and enhances the T cell response to an encephalitogenic peptide of myelin basic protein.
In a murine model of T cell-mediated autoimmune disease, experimental autoimmune encephalitis (EAE), 80% of all encephalitogenic T cell clones in H-2u mice use the V beta 8.2 TCR element. To induce EAE in susceptible strains of mice either heat-killed Bordetella pertussis organisms or Bordetella pertussis toxin (PT) must be injected in addition to Ag in CFA. We investigated the mechanisms by which PT facilitates the induction of EAE. Our data show, that PT interferes with the induction of Ag-induced peripheral T cell anergy. Furthermore it has a specific adjuvanticity for the autoantigen pAc1-11 in vivo and acts as a selective mitogen in vitro. We also tested the hypothesis that PT is a bacterial superantigen that specifically expands the V beta 8.2+ subset of T cells, thereby expanding the encephalitogenic T cell clones that are contained in this subset, so that the number of autoreactive T cells is brought over a critical threshold, necessary to induce autoimmune disease. Our data show that PT is not a superantigen. Staphylococcal enterotoxin B, a V beta 8.2-specific superantigen, does not enhance the immune response to the encephalitogenic peptide.
Kamradt
T
T
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
Soloway
P D
PD
Perkins
D L
DL
Gefter
M L
ML
D000276:Adjuvants, Immunologic; D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D003208:Concanavalin A / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology; D015870:Gene Expression; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000737:chemistry / Q000276:immunology*; D009211:Myoglobin / Q000276:immunology; D010455:Peptides / Q000276:immunology; D037342:Pertussis Toxin; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D010566:Virulence Factors, Bordetella / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D004768:Enterotoxins; D007376:Interleukin-2; D004676:Myelin Basic Protein; D009211:Myoglobin; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D010566:Virulence Factors, Bordetella; D003208:Concanavalin A; C031818:enterotoxin B, staphylococcal; D037342:Pertussis Toxin