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The innate cytokine il-18 inhibits cns autoimmunity through preferential activation of protective cd8 t-cells Jeremy A Morrissette
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Morrissette, Jeremy A., author.
- Language:
- English
- Subjects (All):
- Immunology.
- Cellular biology.
- Pathology.
- 0982.
- 0379.
- 0571.
- Local Subjects:
- Immunology.
- Cellular biology.
- Pathology.
- 0982.
- 0379.
- 0571.
- Genre:
- Academic theses
- Physical Description:
- 1 online resource (106 pages)
- Contained In:
- Dissertations Abstracts International 87-12B
- Place of Publication:
- Ann Arbor : ProQuest Dissertations and Theses, 2026
- Language Note:
- English
- Summary:
- Chronic innate immune activation is widely thought to challenge self-tolerance. IL-18 is an innate, inflammasome-activated cytokine and potent amplifier of T-cell activation. In excess, IL-18 is associated with certain autoinflammatory, but not autoimmune, diseases. We tested how excess IL-18 affected susceptibility to experimental autoimmune encephalomyelitis (EAE), a model of CNS autoimmunity driven by IL-18 responsive, myelin-autoreactive CD4T-cells (CD4Tauto). Prior data suggested that IL-18 would exacerbate immunopathology in EAE. Instead, excess IL-18 was profoundly protective. Excess IL-18 did not impair CD4Tauto priming or early expansion. Rather, it selectively restricted later accumulation of highly activated, splenic CD4Tauto bearing CNS-homing integrins. Despite high IL-18 receptor expression on CD4Tauto and FOXP3+ CD4Treg, excess IL-18 acted specifically through mature CD8T-cells to promote a highly activated CD8Teffector phenotype and IFNγ-dependent protection from EAE. Therapeutic administration of a "decoy-resistant" IL-18 agonist (DR-18) to wild-type mice, even after CD4Tauto expansion, engaged CD8T-cells to diminish CD4Tauto abundance, prevent CNS infiltration, and block immunopathology. Together, these findings demonstrate the unexpected, dominant ability of IL-18 to mobilize protective CD8T-cells against highly activated CD4Tauto and protect from CNS autoimmune pathology; illustrating a potential therapeutically relevant mechanism by which autoinflammation actively opposes autoimmunity
- Notes:
- Source: Dissertations Abstracts International, Volume: 87-12, Section: B.
- Advisors: Canna, Scott W. Committee members: Jordan, Martha S.; Hunter, Christopher A.; Bar-Or, Amit; Anguera, Montserrat C.
- Ph.D. University of Pennsylvania 2026
- Vendor supplied data
- Local Notes:
- School code: 0175
- ISBN:
- 9798247983095
- Access Restriction:
- Restricted for use by site license
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