Subretinal Injection of HY Peptides Induces Systemic Antigen-Specific Inhibition of Effector CD4+ and CD8+ T-Cell Responses
PurposeInjection 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 pro...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00504/full |
| _version_ | 1819030764297125888 |
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| author | Julie Vendomèle Safa Dehmani Quentin Khebizi Anne Galy Sylvain Fisson |
| author_facet | Julie Vendomèle Safa Dehmani Quentin Khebizi Anne Galy Sylvain Fisson |
| author_sort | Julie Vendomèle |
| collection | DOAJ |
| description | PurposeInjection 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.MethodsUbiquitously 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.ResultsImmune 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.ConclusionTaken 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. |
| first_indexed | 2024-12-21T06:35:20Z |
| format | Article |
| id | doaj.art-b0f9413c9ac843eb9a4fb74dbc8d4bb8 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-21T06:35:20Z |
| publishDate | 2018-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b0f9413c9ac843eb9a4fb74dbc8d4bb82022-12-21T19:12:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-03-01910.3389/fimmu.2018.00504332246Subretinal Injection of HY Peptides Induces Systemic Antigen-Specific Inhibition of Effector CD4+ and CD8+ T-Cell ResponsesJulie Vendomèle0Safa Dehmani1Quentin Khebizi2Anne Galy3Sylvain Fisson4Généthon, Inserm UMR_S951, Univ Evry, Université Paris Saclay, EPHE, Evry, FranceGénéthon, Inserm UMR_S951, Univ Evry, Université Paris Saclay, EPHE, Evry, FranceGénéthon, Inserm UMR_S951, Univ Evry, Université Paris Saclay, EPHE, Evry, FranceGénéthon, Inserm UMR_S951, Univ Evry, Université Paris Saclay, EPHE, Evry, FranceGénéthon, Inserm UMR_S951, Univ Evry, Université Paris Saclay, EPHE, Evry, FrancePurposeInjection 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.MethodsUbiquitously 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.ResultsImmune 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.ConclusionTaken 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.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00504/fullanterior chamber-associated immune deviationeyeocular immune privilegesubretinal-associated immune inhibitionT-cells |
| spellingShingle | Julie Vendomèle Safa Dehmani Quentin Khebizi Anne Galy Sylvain Fisson Subretinal Injection of HY Peptides Induces Systemic Antigen-Specific Inhibition of Effector CD4+ and CD8+ T-Cell Responses Frontiers in Immunology anterior chamber-associated immune deviation eye ocular immune privilege subretinal-associated immune inhibition T-cells |
| title | Subretinal Injection of HY Peptides Induces Systemic Antigen-Specific Inhibition of Effector CD4+ and CD8+ T-Cell Responses |
| title_full | Subretinal Injection of HY Peptides Induces Systemic Antigen-Specific Inhibition of Effector CD4+ and CD8+ T-Cell Responses |
| title_fullStr | Subretinal Injection of HY Peptides Induces Systemic Antigen-Specific Inhibition of Effector CD4+ and CD8+ T-Cell Responses |
| title_full_unstemmed | Subretinal Injection of HY Peptides Induces Systemic Antigen-Specific Inhibition of Effector CD4+ and CD8+ T-Cell Responses |
| title_short | Subretinal Injection of HY Peptides Induces Systemic Antigen-Specific Inhibition of Effector CD4+ and CD8+ T-Cell Responses |
| title_sort | subretinal injection of hy peptides induces systemic antigen specific inhibition of effector cd4 and cd8 t cell responses |
| topic | anterior chamber-associated immune deviation eye ocular immune privilege subretinal-associated immune inhibition T-cells |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00504/full |
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