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Tissue barriers, immunosuppressive microenvironments, and privileged sites: the eye's point of view
1Schepens Eye Research Institute, Boston, MA 02114.
Immune privilege exists at numerous sites in the body. It is becoming increasingly clear that privilege is extended to foreign tissues implanted at privileged sites by active regulatory mechanisms, rather than because implanted tissues are hidden from recognition by cells of the immune system. Recent experimental analysis of privilege has focused on regional tissue factors that participate in creating the privileged status. Local barriers are being more fully described, barriers that restrict, but do not prevent, afferent and efferent communication between a privileged site and the systemic immune apparatus. In addition, cytokines and mediators are being discovered at local sites, and these agents appear to create novel microenvironments that act on migrating cells of the lymphoreticular system and thereby modify both the induction and expression of immunity to antigenic materials that are introduced into, or arise within, privileged sites. This review summarizes many recent studies, and attempts to place in the broader context of systemic immunity what has been learned in the recent past about the unique forms of immunity that attend foreign tissue grafts and other types of antigenic materials placed experimentally in privileged sites. Particular emphasis is placed on reconciling (a) the requirements of various organs and tissues for immune protection against invading pathogens with (b) the vulnerability of certain organs and tissues to immunopathogenic processes that inadvertently inflict tissue injury and dysfunction.
Immune privilege exists at numerous sites in the body. It is becoming increasingly clear that privilege is extended to foreign tissues implanted at privileged sites by active regulatory mechanisms, rather than because implanted tissues are hidden from recognition by cells of the immune system. Recent experimental analysis of privilege has focused on regional tissue factors that participate in creating the privileged status. Local barriers are being more fully described, barriers that restrict, but do not prevent, afferent and efferent communication between a privileged site and the systemic immune apparatus. In addition, cytokines and mediators are being discovered at local sites, and these agents appear to create novel microenvironments that act on migrating cells of the lymphoreticular system and thereby modify both the induction and expression of immunity to antigenic materials that are introduced into, or arise within, privileged sites. This review summarizes many recent studies, and attempts to place in the broader context of systemic immunity what has been learned in the recent past about the unique forms of immunity that attend foreign tissue grafts and other types of antigenic materials placed experimentally in privileged sites. Particular emphasis is placed on reconciling (a) the requirements of various organs and tissues for immune protection against invading pathogens with (b) the vulnerability of certain organs and tissues to immunopathogenic processes that inadvertently inflict tissue injury and dysfunction.