Opposite role for interleukin-4 and interferon-gamma on CD30 and lymphocyte activation gene-3 (LAG-3) expression by activated naive T cells.
Polarized human type 1 and type 2 T helper cells not only produce different sets of cytokines, but they also preferentially express certain activation markers, such as lymphocyte activation gene-3 (LAG-3) and CD30, respectively. In this study we have examined the LAG-3 and CD30 expression in relation to the lineage commitment of human naive CD4+ T cells, as assessed at the single-cell level of committed T cells. Purified CD45RA+ umbilical cord blood T lymphocytes were activated with phytohemagglutinin and interleukin (IL)-2 in the absence or presence of interleukin IL-4 or IL-12 and assessed for CD30 and LAG-3 expression, as well as for intracellular cytokine synthesis. Significant numbers of CD30+ cells were only found in CD4+ and CD8+ T lymphocytes of cultures primed with IL-4, which developed into cells able to produce IL-4 and IL-13 in addition to interferon (IFN)-gamma. By contrast, LAG-3 expression was strongly up-regulated in CD4+ and CD8+ T cells from cultures primed with IL-12, which developed into high numbers of IFN-gamma producers. The addition of a neutralizing anti-IFN-gamma antibody to IL-12-primed CD4+ T cell cultures virtually abolished the development of LAG-3-expressing CD4+ T cells. Taken together, these data suggest that CD30 expression is dependent on the presence of IL-4, whereas LAG-3 expression is dependent on the production of IFN-gamma during the lineage commitment of human naive T cells.
Annunziato
F
F
Istituto di Medicina Interna e Immunoallergologia, University of Florence, Italy.
Manetti
R
R
Cosmi
L
L
Galli
G
G
Heusser
C H
CH
Romagnani
S
S
Maggi
E
E
D015703:Antigens, CD; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D017730:Ki-1 Antigen / Q000502:physiology*; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D000093322:Lymphocyte Activation Gene 3 Protein
D015703:Antigens, CD; D017730:Ki-1 Antigen; D008565:Membrane Proteins; D015847:Interleukin-4; D007371:Interferon-gamma; D000093322:Lymphocyte Activation Gene 3 Protein; C000720326:Lag3 protein, human