Mucosal epithelial cells are increasingly recognized as enigmatic modulators of immune responses under pathologic conditions. This effect is mediated in part by aberrant MHC-II expression that is thought to promote peripheral tolerance.
59,60 Leukocytes can also transfer loaded peptide–MHC-II complexes to other cells via exosomes.
61,62 However, MHC-II expression on mucosal epithelial cells is not likely from exogenous sources, as evidence corroborates the ability of mucosal epithelial cells and other nonhematopoietic cells to independently process and present antigen through MHC-II.
60 Briefly, mucosal epithelial cells express the MHC-II transcriptional coactivator (CIITA) and various MHC-II alleles following IFNγ stimulation in vitro.
60,63 In addition, mucosal epithelial cells can also secrete immunomodulatory exosomes containing peptide–MHC-II complexes following IFNγ stimulation.
64 While MHC-II expression has been documented in the corneal epithelium following HSV-1 infection,
65–68 our study is the first to directly show a functional immunologic consequence of MHC-II expression in CECs using an HSV-independent model antigen system. Specifically, we show that MHC-II
+ CECs exhibit functional antigen-presenting capacities to naive CD4 T cells using an in vitro OT-II/OVA
323-339 peptide model. A similar study has shown that CD4 T cell priming by airway epithelial cells promotes a FoxP3
+ regulatory T cell phenotype.
69 Results from the current investigation show that CECs have limited ability to induce FoxP3 expression in naive OT-II CD4 T cells. However, interactions between naive CD4 T cells and MHC-II
+ CECs are unlikely to occur in vivo. Nonetheless, coexpression of MHC-II and PD-L1/CD86 on CECs, as observed in this study, may protect the cornea in situ by tolerizing infiltrating effector CD4 T cells. The functional implication of MHC-II expression by CECs necessitates further study to discern its impact on ocular surface disease.