Protection from experimental autoimmune encephalomyelitis (EAE): non-depleting anti-CD4 mAb treatment induces peripheral T-cell tolerance to MBP in PL/J mice.
Following pre-treatment with a non-depleting anti-CD4 mAb (H129.19) that produces long-lasting receptor saturation, PL/J mice were fully protected from experimental auto-immune encephalomyelitis (EAE) induced by injection of myelin basic protein (MBP). These mice did not develop EAE following MBP re-challenge 5-10 weeks later when the CD4+ cells were no longer coated by the mAb and their lymph node cells were specifically unresponsive to MBP stimulation in vitro. Moreover, superantigen staphylococcal enterotoxin B (SEB) inoculation, which re-induces EAE in MBP immunized mice, failed to activate encephalitogenic T-cells in anti-CD4 + MBP treated mice, even after MBP re-challenge, indicating that tolerance in the peripheral T-cell compartment was achieved. However, MBP re-challenge 16 weeks later, but not SEB, produced an acute episode of EAE in these mice, while it failed to induce disease in a parallel group of adult thymectomized mice. These results indicate that no memory of the first priming exists at this time and that new MBP-specific T-cell precursors are peripheralized and produce EAE after MBP recognition.
Biasi
G
G
Institute of Experimental Pathology, University of Ancona, Italy. oncology@cribi1.bio.unipd.it
Facchinetti
A
A
Monastra
G
G
Mezzalira
S
S
Sivieri
S
S
Tavolato
B
B
Gallo
P
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D004198:Disease Susceptibility; D004361:Drug Tolerance; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control*; D004768:Enterotoxins / Q000276:immunology; D005260:Female; D007108:Immune Tolerance; D051379:Mice; D008815:Mice, Inbred Strains; D004676:Myelin Basic Protein / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000473:pathology; D013934:Thymectomy; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D004768:Enterotoxins; D004676:Myelin Basic Protein; C031818:enterotoxin B, staphylococcal