GSE134278
Comparison of transcriptional profiles from 2W1S-specific CD4+ T cells during 2W1S-expressing Salmonella and Strongyloides ratti infections reveals that infectious context drives effector CD4+ T cell function
Approximately one-third of the world is infected with parasitic helminths, and there are no available vaccines. Helminths induce robust type 2 immune responses and host CD4+ T cells are required for clearance, but how helminth-specific CD4+ T cells are generated and whether they adopt prototypical features of effector Th2 cells is entirely unknown. We generated a novel transgenic line of Strongyloides ratti to track and study  helminth-specific T cells. This transgenic line, termed Hulk, stably expresses immunodominant T cell epitope 2W1S as a fusion protein with FLAG and green fluorescent protein (GFP). We consistently observe expansion of CD44hiCD11ahi 2W1S-specific CD4+ T cells in the lungs of Hulk-infected C57BL/6 mice. Surprisingly, these cells do not exhibit a Th2 or regulatory T cell (Treg) phenotype, and their expansion is minimal compared to expansion following 2W1S-peptide immunization. In order to more thoroughly interrogate the phenotype and function of 2W1S-specific CD4+ T cells during Hulk infection, we performed mRNA sequencing on 2W1S-specific CD4+ T cells from both Hulk-infected and 2W-Salmonella-infected mice. Interestingly, whereas 2W1S-specific CD4+ T cells that expand during 2W-Salmonella infection express canonical pro-inflammatory genes, 2W1S-specific CD4+ T cells from Hulk-infected mice preferentially upregulate genes associated with immune suppression and wound healing. Altogether, these data suggest that helminth antigen specific CD4+ T cells may comprise an unconventional subset that mediates immunosuppression and tissue repair following helminth infection and not necessarily type 2 cytokine responses. Overall design: Mice were infected with 2W1S-expressing S. ratti (Hulk, 15 mice) or Salmonella (Salm, 10 mice). Activated, 2W1S+CD62Llo CD4+ T cells (2W) were electronically sorted from mice in each group and pooled into 3 biological replicates for mRNA sequencing. Naive, 2W1S-CD62Lhi CD4+ T cells (N) were isolated in the same manner from mice in each group as internal naive controls and were pooled into 3 biological replicates in the same manner as the 2W samples for mRNA sequencing.