Persistence of pathogenic CD4+ Th1-like cells in vivo in the absence of IL-12 but in the presence of autoantigen.

摘要: Despite recent successful treatment of murine autoimmune disease with anti-IL-12 mAb, it has not yet been addressed whether mAb can also be effective in late stages and provide lasting protection against recurrence, especially during continued presence autoantigen. We used a newly developed psoriasis model scid/scid mice, which allows easy tracking pathogenic T cells, to show that when is given for 2 wk (1 mg/wk) the stage severe disease, inflammation greatly reduced, as measured by ear thickness histology (scores, 1.1 ± 0.1 vs 2.0 0.4). Moreover, prolonged (4 wk) chronic psoriatic mice high doses mg/wk; active anti-inflammatory (PAAIT)) results almost complete resolution lesions 0.3 2.7 0.2). Surprisingly, however, despite these significant results, psoriasis-like return soon after discontinued. This rapid relapse may attributed large populations activated CD4 + cells present lymph nodes PAAIT animals still expressing an effector/memory phenotype (CD45RB low , L-selectin ). Upon stimulation vitro such node secrete amounts IFN-γ (129 ng/ml); transferred into naive they are able rapidly induce without costimulation. Our data indicates alternative IL-12-independent pathway Th-1-like vivo phase persist maintain their pathogenicity draining tissue site.