Abstract
Injection of an antigen into the anterior chamber of the eye induces a peripheral antigen-specific immune modulation mechanism, known as anterior chamber-associated immune deviation (ACAID). Delayed-type hypersensitivity experiments argue that the subretinal space (SR) of the eye displays properties similar to ACAID. However, no investigation was performed regarding the differential impact of a subretinal antigen injection on peripheral CD4+ versus CD8+ T cells, on the potential immune deviation regarding Th profiles, and on the antigen-specificity of the inhibition. A better understanding of these mechanisms is crucial to improve safety and immunomonitoring of ongoing therapeutic approaches targeting the SR. The aim of this study is to characterize the proliferative capacities and cytokine patterns of antigen-specific CD4+ and CD8+ T cells after a subretinal injection of antigen in mice. Ubiquitously Transcribed tetratricopeptide repeat gene Y-linked (UTY) and DEAD Box polypeptide 3 Y-linked (DBY) peptides which respectively include MHCI- and MHCII-restricted T-cell epitopes of the mouse HY male antigen, were injected into the subretinal space of C57BL/6 female mice. 2 weeks later, these mice were immunized subcutaneously with these peptides and compared to control mice. A week later, T-cell immune responses were analyzed by IFNγ ELISpot assays and cytokine measurements (IL-2, IL-4, IL-6, IL-10, IL-13, IL-17a, IFNγ, TNFα, GM-CSF, and MCP-1) in the spleen and with proliferation assays in draining lymph nodes. Immune cells from mice that received HY peptides in the SR before immunization, compared with those from control immunized mice, secreted significantly smaller quantities of Th1/Tc1, Th2/Tc2, and Th17/Tc17 cytokines, and HY-specific CD4+ T cells proliferated less in response to HY peptides. Taken together, our data clearly demonstrate that the subretinal injection of HY peptides induces a systemic HY-specific inhibition of conventional Th profiles and CD8+ T cells. We propose to call this phenomenon SRAII, for subretinal-associated immune inhibition.
Highlights
In recent decades, the eye has been considered an immuneprivileged site due to its unique anatomical and immune properties
The anterior chamber of the eye is known for its induction of antigen-specific peripheral modulation of the immune response after antigen injection, a characteristic that has been considered unique to this organ
Our results clearly show that the subretinal injection of peptides induces an antigen-specific inhibition of CD4+ T-cell proliferation and a global inhibition of proinflammatory cyto kines, Th1/Tc1, Th2/Tc2, and Th17/Tc17 pro files
Summary
The eye has been considered an immuneprivileged site due to its unique anatomical and immune properties. At least 30 of these have administered treatment via subretinal injections These trials appear to meet safety criteria, the impossibility of immune monitoring of cells other than peripheral blood cells has prevented an in-depth investigation of the immunologic mechanisms involved in these innovative approaches. These therapies, which involve the injection of multicellular or multiprotein components, may well trigger and affect the immune properties of the eye, especially as these treatments are administered in diseased eyes
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