Conjunctival antigen presenting cells: Sentinels for ocular surface inflammation

Abstract Purpose To evaluate the role of conjunctival antigen presenting cells (APC) in experimental dry eye disease (EDE) and in the immune rejection of corneal allografts. Methods Ocular surface APC were depleted by subconjunctival injection of liposomes containing clodronate. APC depletion was confirmed by immunohistochemistry using anti‐CD11c (dendritic cells) and anti‐Iba1 (macrophages) antibodies. EDE was induced by exposing mice to desiccating stress (DS) for 5 days and pathogenic CD4+ T cells were to T cell‐deficient nude mice. Experiments were also performed in a murine model of keratoplasty. Results Injection of clodronate liposomes produced 65% and 86% reductions in conjunctival macrophages and DC respectively. Depletion of APC prior to DS inhibited the generation of autoreactive CD4+ T cells and prevented EDE. APC deletion in nude mice prior to their receiving EDE‐producing CD4+ T cells significantly mitigated EDE. APC depletion prior to keratoplasty completely prevented corneal allograft rejection. However, depleting APC in nude mice prior to transferring CD4+ T cells did not affect corneal allograft rejection indicating that primed CD4+ T cells do not require secondary activation by APC to mediate graft rejection. Conclusion Ocular surface APC play an important role in the generation of autoreactive pathogenic CD4+ T cells that mediate EDE and for secondary activation of these cells at sites of ocular surface inflammation. Ocular surface APC are also crucial for the induction of corneal allograft rejection, but secondary activation of previously primed allospecific CD4+ T cells by resident ocular surface APC is not required. Targeting ocular surface APC may be a facile therapeutic modality for managing ocular surface inflammation.