The nature of antigen in the eye has a profound effect on the cytokine milieu and resultant immune response.
The eye is endowed with a number of mechanisms that protect it from immune-mediated injury. One such mechanism, termed anterior chamber-associated immune deviation (ACAID), evokes the antigen-specific, systemic down-regulation of Th1 responses to antigen inoculated into the anterior chamber of the eye. ACAID has been correlated with the selective production of IL-10 by the antigen-presenting cells (APC) and the development of a cross-regulatory Th2-like response. A small subset of antigens do not induce ACAID, but instead provoke IL-12 and normal Th1 immunity. Remarkably, all soluble antigens tested are capable of inducing ACAID; only cell-associated antigens do not induce ACAID. We hypothesized that the nature of antigen plays a decisive role in the resultant immune response. This hypothesis was tested with two well-characterized antigens, ovalbumin (OVA) and SV40 large T antigen (SV40 Lg T Ag). The soluble forms of OVA and SV40 Lg T Ag induced ACAID in both in vivo and in vitro models of the eye. In contrast, the particulate forms of these antigens, i.e. OVA passively absorbed onto inert latex beads (OVA-latex) and SV40 Lg T Ag expressed in two different cell lines, 99E1 and SV-T2, did not induce ACAID in either in vivo or in vitro models of the eye. In addition, the cytokine profiles of ocular APC pulsed with OVA or OVA-latex showed that soluble OVA induced the production of IL-10, whereas OVA-latex induced the production of IL-12. These data suggest that the nature of the antigen in the eye, whether soluble or particulate, is a crucial determinant in the resultant immune response. Moreover, they suggest a mechanism in which soluble antigens preferentially induce the release of ACAID-inducing IL-10 whereas particulate antigens preferentially induce the release of Th1-inducing IL-12 by responding APC.
D'Orazio
T J
TJ
Graduate Program in Immunology, University of Texas Southwestern Medical Center, Dallas 75235-9057, USA.
Niederkorn
J Y
JY
D000818:Animals; D000867:Anterior Chamber / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000378:metabolism; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology*; D000957:Antigens, Viral, Tumor / Q000008:administration & dosage / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D007267:Injections; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010316:Particle Size; D013539:Simian virus 40 / Q000276:immunology; D012995:Solubility; D014407:Tumor Cells, Cultured
D000941:Antigens; D000957:Antigens, Viral, Tumor; D016207:Cytokines; D010047:Ovalbumin