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 in vitro-differentiated Th populations. For in vivo-differentiated Th subsets, little is known about the heterogeneity of cytokine production in single cells. We recently described a molecule, T1/ST2, that is preferentially expressed on the surface of Th2 cells. Here we combined high-gradient magnetic cell separation with four-color single-cell cytometry to analyze simultaneously three intracellular cytokines and T1/ST2 surface expression on CD4+ cells from lungs containing granulomas induced by Schistosoma mansoni eggs. T1/ST2 was highly up-regulated on CD4+ T cells from hepatic granulomas and granulomatous lungs. T1/ST2+ cells from granulomatous lungs preferentially produced type 2 cytokines ex vivo. In the total CD4+ population, coexpression of type 1 and type 2 cytokines occurred frequently. However, such 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 indicate that individual CD4+ T cells in vivo have different levels of commitment to a certain Th phenotype. Coexpression of two type 2 cytokines or production of one type 2 cytokine together with surface expression of T1/ST2 indicate advanced commitment to the Th2 phenotype.
Löhning
M
M
Deutsches Rheumaforschungszentrum, Berlin, Germany.
Grogan
J L
JL
Coyle
A J
AJ
Yazdanbakhsh
M
M
Meisel
C
C
Gutierrez-Ramos
J C
JC
Radbruch
A
A
Kamradt
T
T
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis*; D015769:Granuloma, Respiratory Tract / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010063:Ovum / Q000276:immunology*; D012550:Schistosoma mansoni / Q000166:cytology / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*
D016207:Cytokines; D008565:Membrane Proteins