Identification of CD4+ T cells with T follicular helper cell characteristics in the pig
Anna Hoog, Sonia Villanueva-Hernández, Mahsa Adib Razavi, Katinka van Dongen, Thomas Eder, Lauriane Piney, Ludivine Chapat, Karelle De Luca, Florian Grebien, Kerstin H. Mair, Wilhelm Gerner
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 hi CD25 - and ICOS dim CD25 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.