Anterior Chamber-Associated Immune Deviation (ACAID): An Acute Response to Ocular Insult Protects from Future Immune-Mediated Damage?

Abstract

The “immune privilege” that inhibits immune defense mechanisms that could lead to damage to sensitive ocular tissue is based on the expression of immunosuppressive factors on ocular tissue and in ocular fluids. In addition to this environmental protection, the injection of antigen into the anterior chamber or infection in the anterior chamber induces a systemic suppression of potentially damaging cell-mediated and humoral responses to the antigen. Here we discuss evidence that suggests that Anterior Chamber-Associated Immune Deviation (ACAID)a is initiated by an ocular response to moderate inflammation that leads to a systemic immunoregulatory response. Injection into the anterior chamber induces a rise in TNF-α and MCP-1 in aqueous humor and an infiltration of circulating F4/80+ monocytes that home to the iris. The induction of ACAID is dependent on this infiltration of circulating monocytes that eventually emigrate to the thymus and spleen where they induce regulatory T cells that inhibit the inductive or effector phases of a cell-mediated immune response. ACAID therefore protects the eye from the collateral damage of an immune response to infection by suppressing a future potentially damaging response to infection.

The in vivo and in vitro induction of anterior chamber associated immune deviation to myelin antigens in C57BL/6 mice

“…In ACAID, the AC injection of particulate antigens caused a rise in TNF-a and MCP-1 in the aqueous humor in addition to the infiltration of circulating F4/80 + monocytes that home to the iris (Cone and Pais, 2009). This infiltration of circulating monocytes controls the process of ACAID induction.…”

Ocular Microbiota and Intraocular Inflammation

“…Antigen injected into these places induces peripheral tolerance to that antigen ( 56 ). A classic phenomenon is the anterior chamber-associated immune deviation (ACAID) in which injection of an antigen to the anterior chamber of the eye induces systemic immunoregulatory responses that are believed to protect the eye from future immune-mediated damage ( 57 ). Similarly, adeno-associated virus delivery to the subretinal space elicits only limited immune response ( 58 , 59 ).…”

Interleukins and cytokine biomarkers in uveitis

“…[ 9 ] ACAID, therefore, protects the eye from collateral damage of an immune response to infection by inducing immune unresponsiveness and systemic antigen-specific immune suppression. [ 10 ]…”