Atopy and Th2‐biased immune responses exacerbate rather than promote corneal allograft survival

Abstract

It is believed that corneal allograft rejection is Th1‐mediated and that directing alloimmune responses toward a Th2 pathway will down‐regulate Th1 responses and promote allograft acceptance. We tested the effect of two Th2‐mediated diseases ‐ allergic conjunctivitis and airway hyperreativity (AHR) ‐ on corneal allograft survival. Allergic conjunctivitis and AHR were induced with short ragweed pollen (SRW) or ovalbumin (OVA). C57BL/6 corneal allografts were transplanted to BALB/c mice with ongoing allergic conjunctivitis or AHR. Mice with conjunctivitis induced with SRW or OVA had exacerbated allograft rejection compared to controls (100% vs 50% rejection; median survival time [MST] = 17 vs. 54 days and 95% vs. 50% rejection; MST = 18 vs. 26 days). SRW‐induced AHR or OVA‐induced AHR exacerbated corneal allograft rejection compared to vehicle controls (94% vs 50% rejection; MST = 21 vs 50 days; and 90% vs. 50% rejection; MST = 20 vs. 56 days). In other experiments, SRW challenge was suspended and mice were challenged 30 days later. Exacerbation of corneal allograft rejection was transient, as there was no difference between SRW‐treated mice and untreated controls (50% rejection; MST >50 days). Thus, atopic diseases are important risk factors in corneal allograft rejection. Tilting the alloimmune response toward a Th2 pathway not only fails to promote corneal allograft survival, but exacerbates immune rejection. Supported by NIH grants EY007641 and EY016664 and Research to Prevent Blindness.