ORCID

https://orcid.org/0000-0002-9433-8939

Date of Award

11-14-2024

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Immunology)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

Tissue-resident T cells play a crucial role in the immune response to neurotropic viral infections and opioid-induced immune disorders. Understanding the roles of tissue-resident T cells in these contexts is essential for developing therapeutic strategies to mitigate their detrimental effects while enhancing their protective functions. The chemokine receptor CXCR6 and its ligand CXCL16 are critical in maintaining the population of tissue-resident T cells in the CNS. CXCR6 is expressed on CD8 T cells that persist in the CNS after recovery from West Nile virus infection. Research has shown that CXCL16, produced by microglia and other myeloid cells, binds to CXCR6 on T cells, facilitating their maintenance and function. CCR2 is another chemokine receptor expressed on a subset of CD8 T cells in the CNS. Transcriptomic analyses of forebrain CCR2+ versus CCR2- CD8 tissue-resident T cells during WNV recovery reveal that CCR2 expression significantly influences hippocampal CD8 TRM phenotype and function, with increased expression of CD103 and IFN-γ. CCR2-deficiency-induced IFN-γ production by tissue-resident T cells worsens recognition memory post-WNV infection. Opioid receptors are expressed on various immune cells, including T cells and microglia. The exploration of KOR signaling sheds light on its impact on opioid-induced immune modulation, offering potential therapeutic targets for managing opioid-induced immune disorders. Through comprehensive analyses, this dissertation advances the understanding of neuroimmune interactions of tissue-resident T cells in the CNS, particularly in the contexts of viral infections and opioid exposure.

Language

English (en)

Chair and Committee

Robyn Klein

Committee Members

Gregory Wu; Brian Edelson; Qingyun Li; Thomas Lane

Available for download on Tuesday, January 13, 2026

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