Antigen Specific CD4+ T Cell Responses against a Gastrointestinal Nematode

Bonnie B Douglas, University of Pennsylvania


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.

Subject Area

Immunology|Molecular biology

Recommended Citation

Douglas, Bonnie B, "Antigen Specific CD4+ T Cell Responses against a Gastrointestinal Nematode" (2021). Dissertations available from ProQuest. AAI28770912.