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 express ion 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 express ion is reportedly restricted to Th1/0 cells and dependent upon IFN-gam ma. We found that, while LAG-3 was expressed only by CD4(+) T cell clo nes 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 in tensity of LAG-3 expression by CD8(+) clones correlated with the amoun t of released IFN-gamma, suggesting that this cytokine is not required for expression but rather for the up-regulation of LAG-3. Flow cytome tric analyses of polyclonal T cell lines confirmed that LAG-3 could be expressed by both CD4(+) and CD8(+) cells that did not contain cytopl asmic 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 L AG-3 and CD30 are selective markers of T cells with type-1 and type-2 cytokine profiles, respectively.