Neuroantigen-specific CD8 T cells inhibit ongoing demyelinating disease by autoregulating CD4 T cell responses using temporally distinct IFNγ- and perforin-dependent mechanisms
| Autor: | Alexander Boyden, Ashley A. Brate, Nitin Karandikar |
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| Rok vydání: | 2018 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 200:163.2-163.2 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.200.supp.163.2 |
| Popis: | Pathogenesis of immune-mediated demyelinating diseases like multiple sclerosis (MS) is thought to be governed by a complex cellular interplay between immunopathological and immunoregulatory responses. We have previously shown that neuroantigen-specific CD8 T cells have an unexpected protective role in the mouse model of MS, experimental autoimmune encephalomyelitis (EAE). In this study, we interrogated the immunotherapeutic potential of PLP178–191-specific CD8 T cells. Here, we show that PLP178–191-specific CD8 T cells, when administered post-disease onset, swiftly ameliorated EAE progression and suppressed PLP178–191-specific CD4 T cell responses as measured by delayed-type hypersensitivity (DTH). To accomplish DTH suppression, PLP178–191-specific CD8 T cells required differential production of perforin and IFNγ. Perforin was ancillary for the rapid suppressive action of PLP178–191-specific CD8 T cells, but was necessary for maintenance of optimal longer term DTH suppression. Conversely, IFNγ production by PLP178–191-specific CD8 T cells was necessary for swift DTH suppression, but was less significant for maintenance of longer term suppression. These data indicate that neuroantigen-specific CD8 T cells employ an ordered regulatory mechanism program over a number of days in vivo during demyelinating disease and have mechanistic implications for this immunotherapeutic approach. |
| Databáze: | OpenAIRE |
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