EXPRESSION AND RELEASE OF LAG-3-ENCODED PROTEIN BY HUMAN CD4(-CELLS ARE ASSOCIATED WITH IFN-GAMMA PRODUCTION() T)

The lymphocyte activation gene (LAG)-3 is a member of the immunoglobul in superfamily that is selectively transcribed in human activated T an d NK cells, In this wort, the possibility that LAG-3 expression by hum an CD4(+) T cells was preferentially related to one or another phenoty pe of cytokine secretion was investigated, Surface LAG-3 expression co rrelated with IFN-gamma, but not IL-4, production in antigen-stimulate d T cells and it was upregulated by IL-12, Most activated CD4(+) T cel l clones with established Th1 or Th0 profiles of cytokine secretion ex pressed LAG-3 on their surface, whereas the great majority of Th2 clon es showed neither surface LAG-3 nor LAG-3 mRNA expression, After activ ation, the majority of CD4+ T cell clones also released soluble LAG-3- related peptides, and such a release correlated positively with the pr oduction of IFN-gamma and inversely with the production of IL-4. Thus, LAG-3 expression by activated CD4+ human T cells appear to be prefere ntially associated with the differentiation/activation pathway leading to the production of IFN-gamma.