Andrew W. Taylor, Ph.D.
A large part of our research effort has been to characterize the immunosuppressive and immunoregulating factors within immune privilege tissues. Through immunochemical and biological analysis of aqueous humor, the fluid filling the anterior chamber of the eye, we have identified several potent immunoregulating and immunosuppressing neuropeptides that 1) suppress the activation of effector Th1 cells, 2) suppress the activation and the inflammatory activity of macrophages, and 3) mediate the induction of antigen-specific regulatory T cells.
Our research has found constitutively present neuropeptides in the immune privileged eye, alpha-melanocyte stimulating hormone (a-MSH), vasoactive intestinal peptide, calcitonin gene related peptide, and somatostatin. Collectively, the neuropeptides in aqueous humor suppress activation of delayed type hypersensitivity of adaptive immunity, and endotoxin activation of macrophages in innate immunity. Individually, the neuropeptides target different cells and stages in the induction of an immune response. Also we have preliminary data suggesting a role for the ocular neuropeptides in the regulation of macrophage functionality in the immune privileged eye.
We are finding that within the ocular microenvironment the activation of macrophages to pathogens does not promote inflammation, but promotes suppressor functionality in the macrophages. These macrophages respond to pathogens without mediating inflammation, or activating T cells. Moreover, the macrophages produce anti-inflammatory cytokines, suppress and possibly induce apoptosis in activated T cells, and produce enzymes associated with wound repair. We have preliminary evidence that this is mediated by neurotransmitters of the sympathetic nervous system, norepinephrine and neuropeptide Y along with a-MSH and somatostatin.
As we continue to examine the mechanisms of ocular immune privilege we further promote the importance of the interactions between the nervous and the immune systems and how we can use these interactions to beneficially manipulate immunity.