Lymphocyte activation gene-3 (LAG-3) expression and IFN-gamma production are variably coregulated in different human T lymphocyte subpopulations.
We evaluated the relationship between cytokine profile and the expression of the lymphocyte activation gene-3 (LAG-3) in both T cell clones and polyclonal T cell lines; LAG-3 is a CD4-like protein whose expression is reportedly restricted to Th1/0 cells and dependent upon IFN-gamma. We found that, while LAG-3 was expressed only by CD4+ T cell clones producing IFN-gamma, most CD8+ clones producing IL-4 but not IFN-gamma (i.e., with a T cytotoxic-2-like profile) were LAG-3+. The intensity of LAG-3 expression by CD8+ clones correlated with the amount of released IFN-gamma, suggesting that this cytokine is not required for expression but rather for the up-regulation of LAG-3. Flow cytometric analyses of polyclonal T cell lines confirmed that LAG-3 could be expressed by both CD4+ and CD8+ cells that did not contain cytoplasmic IFN-gamma. In these cell lines, large proportions of CD4+ and CD8+ cells coexpressed LAG-3 and CD30, a putative marker of Th2-like cells. Overall, our data do not support the earlier suggestion that LAG-3 and CD30 are selective markers of T cells with type-1 and type-2 cytokine profiles, respectively.
Scala
E
E
Department of Clinical Medicine, University of Rome La Sapienza, Italy.
Carbonari
M
M
Del Porto
P
P
Cibati
M
M
Tedesco
T
T
Mazzone
A M
AM
Paganelli
R
R
Fiorilli
M
M
D000595:Amino Acid Sequence; D015703:Antigens, CD; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D002999:Clone Cells; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000502:physiology; D015847:Interleukin-4 / Q000096:biosynthesis; D017730:Ki-1 Antigen / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000235:genetics*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; 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