Critical Role for IL-4 in the Development of Transplant Arteriosclerosis in the Absence of CD40-CD154 Costimulation

摘要: Blockade of the CD40-CD154 pathway can inhibit CD4+ T cell activation but is unable to prevent immune responses mediated by CD8+ cells. However, even in absence cells, inhibition insufficient development transplant arteriosclerosis. This study investigated mechanisms arteriosclerosis CD40 pathway. C57BL/6 CD40−/− (H2b) recipients were transplanted with MHC-mismatched BALB/c (H2d) aortas. Transplant was evident both and CD40+/− mice (intimal proliferation 59 ± 5% for vs 58 4% mice) presence or cells 46 7% anti-CD8-treated 50 10% mice), confirming that are not essential effector this disease. In depleted number eosinophils infiltrating graft markedly increased (109 24 eosinophils/grid 28 7 mice). The correlated augmented intragraft production IL-4. To test hypothesis IL-4 responsible intimal proliferation, CD8 cell-depleted treated anti-IL-4 mAb. resulted significantly reduced eosinophil infiltration into (12 5 anti-CD8+, anti-IL-4-treated 109 eotaxin, CCR3 mRNA production, level (18 anti-CD8+-, conclusion, elevated results an infiltrate important mechanism cell-independent costimulation.