Expression of T-Bet, Eomesodermin, and GATA-3 Correlates With Distinct Phenotypes and Functional Properties in Porcine ?? T Cells.

ABSTRACT: Unlike mice and humans, porcine ?? T cells represent a prominent subset of T cells in blood and secondary lymphatic organs. GATA-3, T-bet and Eomesodermin (Eomes) are transcription factors with crucial functions in T-cell development and functional differentiation, but their expression has not been investigated in porcine ?? T cells so far. We analyzed the expression of these transcription factors in ?? thymocytes, mature ?? T cells from blood, spleen, lymph nodes, and lung tissue as well as in vitro stimulated ?? T cells on the protein level by flow cytometry. GATA-3 was present in more than 80% of all ??-thymocytes. Extra-thymic CD2- ?? T cells expressed high levels of GATA-3 in all investigated organs and had a CD8?-/dimCD27+perforin- phenotype. T-bet expression was mainly found in a subset of CD2+ ?? T cells with an opposing CD8?highCD27dim/-perforin+ phenotype. Eomes+ ?? T cells were also found within CD2+ ?? T cells but were heterogeneous in regard to expression of CD8?, CD27, and perforin. Eomes+ ?? T cells frequently co-expressed T-bet and dominated in the spleen. During aging, CD2-GATA-3+ ?? T cells strongly prevailed in young pigs up to an age of about 2 years but declined in older animals where CD2+T-bet+ ?? T cells became more prominent. Despite high GATA-3 expression levels, IL-4 production could not be found in ?? T cells by intracellular cytokine staining. Experiments with sorted and ConA + IL-2 + IL-12 + IL-18-stimulated CD2- ?? T cells showed that proliferating cells start expressing CD2 and T-bet, produce IFN-?, but retain GATA-3 expression. In summary, our data suggest a role for GATA-3 in the development of ??-thymocytes and in the function of peripheral CD2-CD8?-/dimCD27+perforin- ?? T cells. In contrast, T-bet expression appears to be restricted to terminal differentiation stages of CD2+ ?? T cells, frequently coinciding with perforin expression. The functional relevance of high GATA-3 expression levels in extra-thymic CD2- ?? T cells awaits further clarification. However, their unique phenotype suggests that they represent a thymus-derived separate lineage of ?? T cells in the pig for which currently no direct counterpart in rodents or humans has been described.

SUBMITTER: Rodriguez-Gomez IM 

PROVIDER: S-EPMC6421308 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature