Expression and release of LAG-3-encoded protein by human CD4+ T cells are associated with IFN-gamma production .
The lymphocyte activation gene (LAG) -3 is a member of the immunoglobulin super-family that is selectively transcribed in human activated T and NK cells. In this work, the possibility that LAG-3 expression by human CD4+ T cells was preferentially related to one or another phenotype of cytokine secretion was investigated. Surface LAG-3 expression correlated with IFN-gamma, but not IL-4, production in antigen-stimulated T cells and it was up-regulated by IL-12. Most activated CD4+ T cell clones with established Th1 or Th0 profiles of cytokine secretion expressed LAG-3 on their surface, whereas the great majority of Th2 clones showed neither surface LAG-3 nor LAG-3 mRNA expression. After activation, the majority of CD4+ T cell clones also released soluble LAG-3-related peptides, and such a release correlated positively with the production of IFN-gamma and inversely with the production of IL-4. Thus, LAG-3 expression by activated CD4+ human T cells appear to be preferentially associated with the differentiation/activation pathway leading to the production of IFN-gamma.
Annunziato
F
F
Istituto di Clinica Medica e Immunollergologia, University of Florence, Italy.
Manetti
R
R
Tomasévic
I
I
Guidizi
M G
MG
Biagiotti
R
R
Giannò
V
V
Germano
P
P
Mavilia
C
C
Maggi
E
E
Romagnani
S
S
D015703:Antigens, CD; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002999:Clone Cells; D017931:DNA Primers; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D017730:Ki-1 Antigen / Q000235:genetics; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D000093322:Lymphocyte Activation Gene 3 Protein
D015703:Antigens, CD; D017931:DNA Primers; D017730:Ki-1 Antigen; D008565:Membrane Proteins; D012333:RNA, Messenger; D007371:Interferon-gamma; D000093322:Lymphocyte Activation Gene 3 Protein; C000720326:Lag3 protein, human; C000720328:soluble LAG-3 protein, human