Corneal Myofibroblasts Suppress T-Cell Immunity in Corneal Transplantation

To evaluate the immunoregulatory effect of corneal myofibroblasts on effector T cells derived from allogeneic corneal transplant recipient mice.

Allo-primed CD4+CD25- effector T cells isolated from the draining lymph nodes of corneal transplant recipient mice were cocultured with corneal myofibroblasts or corneal fibroblasts. Flow cytometry was used to measure effector T-cell activation and function by expression of CD69, CD40L, and IFN-γ. Flow cytometry was also used to quantify T-cell apoptosis and T-cell proliferation upon coculture with corneal myofibroblasts.

Coculturing effector T cells with corneal myofibroblasts led to a significant decrease in effector T-cell activation as assessed by T-cell expression of CD69 (5520 ± 373 vs. 1701 ± 140) and CD40L (127.50 ± 4.17 vs. 42.87 ± 2.63) mean fluorescence intensity; this suppression was not seen with corneal fibroblasts. Coculture of T cells with myofibroblasts additionally led to a significant reduction in the frequency of IFN-γ+ effector T cells compared to coculture with fibroblasts (2.94% ± 0.85% vs. 0.65% ± 0.23%). Finally, compared to fibroblasts, coculture with myofibroblasts led to a significant increase in the frequency of apoptotic effector T cells (14.78% ± 3.67% vs. 32.48% ± 5.43%) and a significant reduction in T-cell proliferation (61.60% ± 2.68% vs. 39.63% ± 0.92%).

Myofibroblasts are capable of suppressing T-cell immunity through suppression of effector T-cell proliferation, activation, and function, as well as the promotion of T-cell apoptosis. Our data suggest that in addition to their well-established role in extracellular matrix production, myofibroblasts may also actively participate in immunoregulation.