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Lymphocyte Activation Gene-3 (LAG-3) Expression and IFN- Production Are Variably Coregulated in Different Human T Lymphocyte Subpopulations¹

Enrico Scala^2,*, Maurizio Carbonari^*, Paola Del Porto, Marina Cibati^*, Tiziana Tedesco^*, Anna Maria Mazzone^*, Roberto Paganelli^* and Massimo Fiorilli^3,*

Departments of ^* Clinical Medicine and Cellular and Developmental Biology, University of Rome ‘La Sapienza’, Rome, Italy

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-. We found that, while LAG-3 was expressed only by CD4⁺ T cell clones producing IFN-, most CD8⁺ clones producing IL-4 but not IFN- (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-, 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-. 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.

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