Antigen specific CD4+ T cell responses against a gastrointestinal nematode / Bonnie B. Douglas.

Format:

Book

Thesis/Dissertation

Author/Creator:

Douglas, Bonnie B., author.

Contributor:

Herbert, De'Broski R., degree supervisor.

University of Pennsylvania. Department of Immunology, degree granting institution.

Language:

English

Subjects (All):

Immunology.

Molecular biology.

Immunology--Penn dissertations.

Penn dissertations--Immunology.

Local Subjects:

Immunology.

Molecular biology.

Immunology--Penn dissertations.

Penn dissertations--Immunology.

Physical Description:

1 online resource (155 pages)

Contained In:

Dissertations Abstracts International 83-08B.

Place of Publication:

[Philadelphia, Pennsylvania] : University of Pennsylvania ; Ann Arbor : ProQuest Dissertations & Theses, 2021.

Language Note:

English

System Details:

Mode of access: World Wide Web.

Summary:

Helminths are distinct from microbial pathogens in terms of size and complexity, and are likely the evolutionary driving force for type 2 immunity. CD4+ helper T cells can both coordinate worm clearance and prevent immunopathology, but issues of T cell antigen specificity in the context of helminth-induced Th2 and T regulatory cell (Treg) responses have not been addressed. Herein, a novel transgenic line of the gastrointestinal nematode Strongyloides ratti was generated that expresses the immunodominant CD4+ T cell epitope 2W1S as a fusion protein with green fluorescent protein (GFP) and FLAG peptide in order to track and study helminth-specific CD4+ T cells. C57BL/6 mice infected with this stable transgenic line (termed Hulk) underwent a dose-dependent expansion of activated CD44+CD11a+ 2W1S-specific CD4+ T cells, preferentially in the lung parenchyma. Transcriptional profiling of 2W1S-specific CD4+ T cells isolated from mice infected with either Hulk or the enteric bacterial pathogen Salmonella expressing 2W1S revealed that pathogen context exerted a dominant influence over CD4+ T cell phenotype. Interestingly, Hulk-elicited 2W1S-specific CD4+ T cells exhibited both Th2 and Treg phenotypes and expressed high levels of the EGFR ligand amphiregulin, which differed greatly from the phenotype of 2W1S-specific CD4+ T cells elicited by 2W1S-expressing Salmonella. While immunization with 2W1S peptide did not enhance clearance of Hulk infection, immunization did increase total amphiregulin production as well as the number of amphiregulin-expressing CD3+ cells in the lung following Hulk infection. Altogether, this new model system reveals that helminth-specific CD4+ T cells can adopt effector as well as immunosuppressive and wound reparative phenotypes. This report establishes a new resource for studying the nature and function of helminth-specific T cells.

Notes:

Source: Dissertations Abstracts International, Volume: 83-08, Section: B.

Advisors: Herbert, De'Broski R.; Committee members: Laufer, Terri; Hunter, Christopher; Beiting, Daniel; Cancro, Michael.

Department: Immunology.

Ph.D. University of Pennsylvania 2021.

Local Notes:

School code: 0175

ISBN:

9798780656319

Access Restriction:

Restricted for use by site license.

This item must not be sold to any third party vendors.