T1/ST2 expression is enhanced on CD4(+) T cells from schistosome egg-induced granulomas: Analysis of Th cell cytokine coexpression ex vivo

Th cells are categorized into subsets based on the cytokine production of i n vitro-differentiated Th populations. For in vivo-differentiated Th subset s, little is known about the heterogeneity of cytokine production in single cells. We recently described a molecule, T1/ST2, that is preferentially ex pressed on the surface of Th2 cells, Here we combined high-gradient magneti c cell separation with four-color single-cell cytometry to analyze simultan eously three intracellular cytokines and T1/ST2 surface-expression on CD4() cells from lungs containing granulomas induced by Schistosoma mansoni egg s. T1/ST2 was highly up-regulated on CD4(+) T cells from hepatic granulomas and granulomatous lungs. T1/ST2(+) cells from granulomatous lungs preferen tially produced type 2 cytokines ex vivo. In the total CD4(+) population, c oexpression of type 1 and type 2 cytokines occurred frequently, However, su ch coproduction was drastically reduced in T1/ST2(+) cells compared with T1 /ST2(-) cells. Coexpression of type 1 and type 2 cytokines was also rare in cells simultaneously producing two cytokines of one type. These findings i ndicate that individual CD4(+) T cells in vivo have different levels of com mitment to a certain Th phenotype. Coexpression of two type 2 cytokines or production of one type 2 cytokine together with surface expression of T1/ST 2 indicate advanced commitment to the Th2 phenotype.