A role for BCL6 in maintaining CX3CR1⁺CD4⁺T cells during helminth infection

Abstract Distinct subsets of T lymphocytes express CX3CR1 under inflammatory conditions, but little is known about CX3CR1 + CD4 + T cells during Type 2 inflammation in helminth infections. Here, we used a fate-mapping mouse model to characterize CX3CR1 + CD4 + T cells during both acute Nippostrongylus brasiliensis and chronic Schistosoma mansoni helminth infections, revealing CX3CR1 + CD4 + T cells to be an activated tissue homing subset with varying capacity for cytokine production. Tracking these cells over time revealed that maintenance of CX3CR1 itself along with a T H 2 phenotype conferred a survival advantage in the inflamed tissue. Single-cell RNA-sequencing analysis of fate-mapped CX3CR1 + CD4 + T cells from both the peripheral tissue and the spleen revealed a considerable level of diversity and identified a distinct population of BCL6 + TCF-1 + PD1 + CD4 + T cells in the spleen during helminth infections. Conditional deletion of BCL6 in CX3CR1 + cells result in fewer CX3CR1 + CD4 + during infection, indicating a role in sustaining CD4 + T cell responses to helminth infections. Overall, our studies revealed the behavior and heterogeneity of CX3CR1 + CD4 + T cells during Type 2 inflammation in helminth infections and identified BCL6 to be important in their maintenance.