Abstract
Anterior chamber-associated immune deviation (ACAID), a manifestation of ocular immune privilege, prevents Th1-dependent delayed hypersensitivity from developing in response to eye-derived Ags, thereby preserving vision. Since Th2-type cells have recently been shown to mediate destructive inflammation of the cornea, we wondered whether pre-emptive induction of ACAID could inhibit Th2 responses. Using a murine model of OVA -specific, Th2-dependent pulmonary inflammation, we pretreated susceptible mice by injecting OVA alone into the anterior chamber, or by injecting OVA-pulsed, TGF-beta2-treated peritoneal exudate cells i.v. These mice were then immunized with OVA plus alum strategy that generates Th2-mediated OVA-specific pulmonary pathology. When pretreated mice were challenged intratracheally with OVA, their bronchoalveolar lavage fluids contained far fewer eosinophils and significantly less IL-4, IL-5, and IL-13 compared with that of positive, nonpretreated controls. Similarly, lung-draining lymph node cells of pretreated mice secreted significantly less IL-4, IL-5, and IL-13 when challenged in vitro with OVA. Moreover, sera from pretreated mice contained much lower titers of OVA-specific IgE Abs. We conclude that Ags injected into the anterior chamber of the eye impair both Th1 and Th2 responses. These results reduce the likelihood that ACAID regulates Th1 responses via a Th2-like mechanism. Thus, immune privilege of the eye regulates inflammation secondary to both Th1- and Th2-type immune responses.
Highlights
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Because the first reports of associated immune deviation (ACAID) arose from tissue transplantation experiments and because delayed hypersensitivity and Th1-type immune responses have come to be considered dominant effectors of graft rejection, virtually all studies of ACAID have emphasized suppression of Th1type immunity as a cardinal feature of the phenomenon
Since Th1 responses were first described as the reciprocal of Th2 responses and since Th2 cells were shown to suppress Th1-type responses [26], various investigators consider ACAID to be merely a Th2 response to Ags introduced into the anterior chamber (AC) of the eye
Summary
ACAID, anterior chamber-associated immune deviation; AC, anterior chamber; BAL, bronchoalveolar lavage; KLH, keyhole limpet hemocyanin; LN, lymph node; PEC, peritoneal exudate cell; i.t., intratracheal. Since Th2 cells are capable of promoting inflammation of the ocular surface that leads to blindness, it is of interest to know whether functionally similar cells have the ability to mediate ACAID, a process that is believed to inhibit the blinding consequences of inflammation To this point, it has recently been demonstrated that ACAID can readily be induced in mice in which the IL-4 gene had been disrupted, a genetic lesion that prevents these mice from acquiring Th2-type responses to exogenous Ags [8, 9]. Our results indicate that mice pretreated with an anterior chamber injection of OVA or with an i.v. injection of OVA-pulsed ACAID-inducing APCs exposed in vitro to TGF-2 [19, 20] acquired OVA-specific ACAID and failed to develop the typical signs of OVA-dependent experimental allergic lung disease These findings exclude the possibility that ACAID is mediated by Th2 regulatory cells
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