Farah Itani

Infection with Neuroantigen-encoding Listeria: Induction of CD8 T Cell Responses and Suppression of Demyelinating Disease
Biography

Elucidating the Mechanisms of Autoregulatory CNS-Specific CD8+ T Cell-Mediated Amelioration of Experimental Autoimmune Encephalomyelitis

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) that afflicts approximately 500,000 individuals within the US. Experimental autoimmune encephalomyelitis (EAE) is the conventional animal model used to study MS, induced by immunization of mice with myelin-related antigens. The etiology of MS remains unknown, and disease is thought to be initiated by the formation of acute inflammatory lesions and an increase in blood-brain barrier permeability. CD4+ T cells, CD8+ T cells, B cells, as well as other immune cells are detected in the inflammatory CNS lesions of MS patients. CD8+ T cells predominate in MS lesions; however, their role remains controversial. Previous research from our lab demonstrated a novel and unexpected regulatory role for CNS-specific CD8+ T cells in both MS and EAE. In the models thus far, CNS-specific CD8+ T cell responses are induced by active immunization with exogenous antigens. One of my projects aims to evaluate whether distinct functionality may be induced in CD8+ responses toward endogenously processed and presented epitopes. This involves the generation of recombinant Listeria monocytogenes strains that express peptides demonstrated to elicit CD8+ T cell responses in EAE. Using the murine model of listeriosis, we propose to investigate whether these CD8+ T cell responses are encephalitogenic or regulatory in nature, and to understand the cellular and molecular interactions that determine this functional differentiation.

Itani FR, Sinha S, Brate AA, Pewe LL, Gibson-Corley KN, Harty JT, Karandikar NJ. Suppression of autoimmune demyelinating disease by preferential stimulation of CNS-specific CD8 T cells using Listeria-encoded neuroantigen. Sci Rep. 2017 May 8;7(1):1519. doi: 10.1038/s41598-017-01771-8. PubMed PMID: 28484224; PubMed Central PMCID: PMC5431563.

Sinha S, Boyden AW, Itani FR, Crawford MP, Karandikar NJ. CD8(+) T-Cells as Immune Regulators of Multiple Sclerosis. Front Immunol. 2015 Dec 10;6:619. doi:10.3389/fimmu.2015.00619. Review. PubMed PMID: 26697014; PubMed Central PMCID:PMC4674574.

Hale M, Itani F, Buchta CM, Wald G, Bing M, Norian LA. Obesity triggers enhanced MDSC accumulation in murine renal tumors via elevated local production of CCL2. PLoS One. 2015 Mar 13; 10(3):e0118784. doi:10.1371/journal.pone.0118784. PMID: 25769110

Sinha S, Itani FR, Karandikar NJ. Immune regulation of multiple sclerosis by CD8+ T cells. Immunol Res. 2014 Aug;59(1-3):254-65. doi:10.1007/s12026-014-8529-9. Review. PubMed PMID: 24845461; PubMed Central PMCID: PMC4125494

Scientist
Cellular Immunology
Johnson & Johnson
Farah Itani