Platelet-derived or soluble CD154 induces vascularized allograft rejection independent
of cell-bound CD154
J. Clin. Invest. He Xu, et al. 116:769 doi:10.1172/JCI27155 [
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Figure 3Soluble rCD154 trimers induce cardiac allograft rejection in CD154-deficient mice. (
A) C57BL/6 recipients accept BALB/c donor heart allografts with (
n = 10) but not without (
n = 10) CD154 blockade using MR-1. Similarly, CD154-KO mice accept cardiac allografts (
n = 14). However, the infusion of human rCD154 trimers (500 μg) induces rejection by CD154-KO recipients (
n = 12;
P < 0.001 versus untreated animals). Human CD154 blockade with the anti-human CD154 antibody 5c8 restores the tolerant phenotype to animals receiving CD154 trimers (
n = 5;
P = 0.002 versus trimer-treated animals). Infusion of trimers into WT animals (
n = 6) accelerated the rate of rejection by an average of 1.4 days (
P = 0.001 versus untreated controls). (
B) Cardiac allografts from CD154-KO recipients that received human rCD154 trimers show acute cellular rejection. Magnification, ×20. (
C) Allografts from CD154-KO recipients treated with 5c8 followed by infusion of human rCD154 trimers show normal myocardium without rejection. Magnification, ×40.
