Identification of CD4+ T cells with T follicular helper cell characteristics in the pig

Abstract

T follicular helper (Tfh) cells provide help to germinal center B cells for affinity maturation, class switch and memory formation. Despite these important functions, this subset has not been studied in detail in pigs due to a lack of species-specific antibodies. We investigated putative Tfh cells from lymphoid tissues and blood of healthy pigs by using cross-reactive antibodies for inducible T-cell costimulator (ICOS) and B-cell lymphoma 6 (Bcl-6). In lymph nodes, we identified a CD4⁺ T cell population with an ICOS⁺Bcl-6⁺CD8α⁺ phenotype, reminiscent of human and murine germinal center Tfh cells. Within blood-derived CD4⁺ T cells, sorted ICOS^hiCD25^- and ICOS^dimCD25^dim cells were able to induce the differentiation of CD21⁺IgM⁺ B cells into Ig-secreting plasmablasts. Compared to naïve CD4⁺ T cells, these two phenotypes were 3- to 7-fold enriched for cells expressing the Tfh-related transcripts CD28, CD40LG, IL6R and MAF, as identified by single-cell RNA sequencing. These results provide a first characterization of Tfh cells in swine and confirm their ability to provide B-cell help.