Neuroantigen-Specific CD4 Cells Expressing Interferon-γ (IFN-γ), Interleukin (IL)-2 and IL-3 in a Mutually Exclusive Manner Prevail in Experimental Allergic Encephalomyelitis (EAE)
Experimental allergic encephalomyelitis (EAE) is mediated by neuroantigen-specific pro-inflammatory T cells of the Th1 and Th17 effector class. Th-17 cells can be clearly defined by expression of IL-17, but not IFN-γ, IL-2 or IL-3. Th1 cells do not express IL-17, but it is unclear presently to what...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2012-08-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2073-4409/1/3/576 |
| _version_ | 1797726119379599360 |
|---|---|
| author | Paul V. Lehmann Maike D. Hesse Stefan Quast Alexey Y. Karulin |
| author_facet | Paul V. Lehmann Maike D. Hesse Stefan Quast Alexey Y. Karulin |
| author_sort | Paul V. Lehmann |
| collection | DOAJ |
| description | Experimental allergic encephalomyelitis (EAE) is mediated by neuroantigen-specific pro-inflammatory T cells of the Th1 and Th17 effector class. Th-17 cells can be clearly defined by expression of IL-17, but not IFN-γ, IL-2 or IL-3. Th1 cells do not express IL-17, but it is unclear presently to what extent they co-express the cytokines canonically assigned to Th1 immunity (i.e., IFN-γ, IL-2 and IL-3) and whether CD4 cells producing these cytokines indeed belong to a single Th1 lineage. It is also unclear to what extent the Th1 response in EAE entails polyfunctional T cells that co-express IFN-γ and IL-2. Therefore, we dissected the Th1 cytokine signature of neuroantigen-specific CD4 cells studying at single cell resolution co-expression of IFN-γ, IL-2 and IL-3 using dual color cytokine ELISPOT analysis. Shortly after immunization, in the draining lymph nodes (dLN), the overall cytokine signature of the neuroantigen-specific CD4 cells was highly type 1-polarized, but IFN-γ, IL-2, and IL-3 were each secreted by different CD4 cells in a mutually exclusive manner. This single cell – single cytokine profile was stable through the course of chronic EAE–polyfunctional CD4 cells co-expressing IL-2 and IFN-γ presented less than 5% of the neuroantigen-specific T cells, even in the inflamed CNS itself. The neuroantigen-specific CD4 cells that expressed IFN-γ, IL-2 and IL-3 in a mutually exclusive manner exhibited similar functional avidities and kinetics of cytokine production, but showed different tissue distributions. These data suggest that Th1 cells do not belong to a single lineage, but different Th1 subpopulations jointly mediate Th1 immunity. |
| first_indexed | 2024-03-12T10:41:13Z |
| format | Article |
| id | doaj.art-f47d980a4b8d4b35af574f80411b24c2 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T10:41:13Z |
| publishDate | 2012-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-f47d980a4b8d4b35af574f80411b24c22023-09-02T08:09:40ZengMDPI AGCells2073-44092012-08-011357659610.3390/cells1030576Neuroantigen-Specific CD4 Cells Expressing Interferon-γ (IFN-γ), Interleukin (IL)-2 and IL-3 in a Mutually Exclusive Manner Prevail in Experimental Allergic Encephalomyelitis (EAE)Paul V. LehmannMaike D. HesseStefan QuastAlexey Y. KarulinExperimental allergic encephalomyelitis (EAE) is mediated by neuroantigen-specific pro-inflammatory T cells of the Th1 and Th17 effector class. Th-17 cells can be clearly defined by expression of IL-17, but not IFN-γ, IL-2 or IL-3. Th1 cells do not express IL-17, but it is unclear presently to what extent they co-express the cytokines canonically assigned to Th1 immunity (i.e., IFN-γ, IL-2 and IL-3) and whether CD4 cells producing these cytokines indeed belong to a single Th1 lineage. It is also unclear to what extent the Th1 response in EAE entails polyfunctional T cells that co-express IFN-γ and IL-2. Therefore, we dissected the Th1 cytokine signature of neuroantigen-specific CD4 cells studying at single cell resolution co-expression of IFN-γ, IL-2 and IL-3 using dual color cytokine ELISPOT analysis. Shortly after immunization, in the draining lymph nodes (dLN), the overall cytokine signature of the neuroantigen-specific CD4 cells was highly type 1-polarized, but IFN-γ, IL-2, and IL-3 were each secreted by different CD4 cells in a mutually exclusive manner. This single cell – single cytokine profile was stable through the course of chronic EAE–polyfunctional CD4 cells co-expressing IL-2 and IFN-γ presented less than 5% of the neuroantigen-specific T cells, even in the inflamed CNS itself. The neuroantigen-specific CD4 cells that expressed IFN-γ, IL-2 and IL-3 in a mutually exclusive manner exhibited similar functional avidities and kinetics of cytokine production, but showed different tissue distributions. These data suggest that Th1 cells do not belong to a single lineage, but different Th1 subpopulations jointly mediate Th1 immunity.http://www.mdpi.com/2073-4409/1/3/576EAE/MSNeuroimmunologyTwo-color ELISPOTDual color ELISPOT Memory T cellsTh1 cellscytokine co-expressionpolyfunctional T cells |
| spellingShingle | Paul V. Lehmann Maike D. Hesse Stefan Quast Alexey Y. Karulin Neuroantigen-Specific CD4 Cells Expressing Interferon-γ (IFN-γ), Interleukin (IL)-2 and IL-3 in a Mutually Exclusive Manner Prevail in Experimental Allergic Encephalomyelitis (EAE) Cells EAE/MS Neuroimmunology Two-color ELISPOT Dual color ELISPOT Memory T cells Th1 cells cytokine co-expression polyfunctional T cells |
| title | Neuroantigen-Specific CD4 Cells Expressing Interferon-γ (IFN-γ), Interleukin (IL)-2 and IL-3 in a Mutually Exclusive Manner Prevail in Experimental Allergic Encephalomyelitis (EAE) |
| title_full | Neuroantigen-Specific CD4 Cells Expressing Interferon-γ (IFN-γ), Interleukin (IL)-2 and IL-3 in a Mutually Exclusive Manner Prevail in Experimental Allergic Encephalomyelitis (EAE) |
| title_fullStr | Neuroantigen-Specific CD4 Cells Expressing Interferon-γ (IFN-γ), Interleukin (IL)-2 and IL-3 in a Mutually Exclusive Manner Prevail in Experimental Allergic Encephalomyelitis (EAE) |
| title_full_unstemmed | Neuroantigen-Specific CD4 Cells Expressing Interferon-γ (IFN-γ), Interleukin (IL)-2 and IL-3 in a Mutually Exclusive Manner Prevail in Experimental Allergic Encephalomyelitis (EAE) |
| title_short | Neuroantigen-Specific CD4 Cells Expressing Interferon-γ (IFN-γ), Interleukin (IL)-2 and IL-3 in a Mutually Exclusive Manner Prevail in Experimental Allergic Encephalomyelitis (EAE) |
| title_sort | neuroantigen specific cd4 cells expressing interferon γ ifn γ interleukin il 2 and il 3 in a mutually exclusive manner prevail in experimental allergic encephalomyelitis eae |
| topic | EAE/MS Neuroimmunology Two-color ELISPOT Dual color ELISPOT Memory T cells Th1 cells cytokine co-expression polyfunctional T cells |
| url | http://www.mdpi.com/2073-4409/1/3/576 |
| work_keys_str_mv | AT paulvlehmann neuroantigenspecificcd4cellsexpressinginterferongifnginterleukinil2andil3inamutuallyexclusivemannerprevailinexperimentalallergicencephalomyelitiseae AT maikedhesse neuroantigenspecificcd4cellsexpressinginterferongifnginterleukinil2andil3inamutuallyexclusivemannerprevailinexperimentalallergicencephalomyelitiseae AT stefanquast neuroantigenspecificcd4cellsexpressinginterferongifnginterleukinil2andil3inamutuallyexclusivemannerprevailinexperimentalallergicencephalomyelitiseae AT alexeyykarulin neuroantigenspecificcd4cellsexpressinginterferongifnginterleukinil2andil3inamutuallyexclusivemannerprevailinexperimentalallergicencephalomyelitiseae |