Role of Th1 and Th2 cells in anterior chamber‐associated immune deviation

Abstract

SUMMARYThe immunological privilege of the anterior chamber (AC) of the eye is due, at least in part, to a selective antigen-specific down-regulation of delayed-type hypersensitivity (DTH) and a normal induction of antibody responses: a phenomenon that has been termed anterior chamber-associated immune deviation (ACAID). This dichotomy in the systemic immune responses is suggestive of a Thelper type-2 (Th2)-dominated immune phenotype in which a Th2 cell population is preferentially activated and cross-regulates T-helper type-1 (Th1) effector elements. This hypothesis was tested by comparing the cytokine pattern of antigen-pulsed spleen cells from mice primed in the anterior chamber with antigens that induce ACAID with responses in hosts primed with antigens that do not induce ACAID. The results indicated that CD4 spleen cells from hosts primed in the AC with antigens that induce ACAID produced significant quantities of interleukin-10 (IL-10) but insignificant levels of IL-2, IL-4 and interferon-g (IFN-g). In contrast, hosts primed in the AC with antigens that do not induce ACAID, but instead elicit normal DTH, displayed cytokine patterns indicative of a Th1 response: significant quantities of IL-2 and IFN-g were produced while IL-4 and IL-10 secretion was insignificantly different from normal controls. The immunological phenotype of the AC-primed hosts could be altered by systemic treatment with antibodies against either a Th1 cytokine (IFN-g) or a Th2 cytokine (IL-10). Hosts treated with anti-IL-10 antibody and subsequently primed in the AC with ACAID-inducing antigens developed normal DTH responses, while hosts treated with anti-IFN-g antibody and primed in the AC with antigens that normally produce positive DTH responses failed to develop positive DTH. Collectively the results support the proposition that immune privilege in the AC of the eye is due to the selective activation of a Th2 population that cross-regulates Th1 responses.

Ocular Immune Privilege Promoted by the Presentation of Peptide on Tolerogenic B Cells in the Spleen. II. Evidence for Presentation by Qa-1

“…However, the suppression of IgG and IgM Ab responses in that study was due to IFN-␥ produced by Qa-1-restricted CD8 ϩ regulatory T cells (10). By contrast, ACAID involves the down-regulation of IFN-␥ and a concomitant induction of IL-10 production (31)(32)(33). In other systems, Qa-1-restricted CD8 ϩ regulatory T cells have been shown to down-regulate Th1 immune responses and mitigate Th1-mediated autoimmune diseases, such as experimental allergic encephalomyelitis (34,35).…”

Immune response following intraocular delivery of recombinant viral vectors

“…Nevertheless, the immune response following intraocular injection of AAV is similar to that described in ACAID (ie, a predominant Th2 like response). [25][26][27]55 One question relating to the AAV-induced humoral response is whether it would be possible to readminister the virus/transgene in the presence of virus-specific antibodies. Studies in mice and in monkeys have demonstrated that these antibodies are not neutralizing and that it is possible to obtain additional transduction events.…”

Oligoadenylate Synthetase/Protein Kinase R Pathways and αβ TCR+ T Cells Are Required for Adenovirus Vector: IFN-γ Inhibition of Herpes Simplex Virus-1 in Cornea

“…We reason this difference may be the case from previous reports examining the immunosuppressive environment of the anterior ocular chamber. Under homeostatic conditions, the anterior chamber of the eye has a specific deficiency of Ag-specific delayed-type hypersensitivity (DTH)-mediating T cells, mediated by Th1 cells, and a shift toward a Th2 phenotype of CD4 ϩ T cells (74). This situation would therefore be different from the normal immune environment in the TG, potentially explaining some of the differences observed in the effect of Ad:IFN-␥ in cornea vs TG.…”