Galectin‐1 functions as a Th2 cytokine that selectively induces Th1 apoptosis and promotes Th2 function

Abstract

Galectin‐1 has been implicated in regulating T‐cell survival, function, and Th1/Th2 balance in several mouse models, though the molecular and cellular basis of its immuno‐modulatory activity has not been completely elucidated. Therefore, we examined galectin‐1 expression and activity within differentiated murine Th1 and Th2 subsets. While recombinant galectin‐1 specifically bound to both T‐cell subsets, Th1 and Th2 T cells expressed distinct combinations of galectin‐1‐reactive epitopes and were differentially responsive to galectin‐1 exposure. Indeed, Th1 cells were more susceptible to galectin‐1‐induced death than Th2 cells. Th2 protection from apoptosis was correlated with expression of anti‐apoptotic galectin‐3. Further, galectin‐1 promoted TCR‐induced type 2 cytokine production by Th2 cells. Differentiated Th2 cells constitutively expressed high levels of galectin‐1 and can be induced to produce even higher levels of galectin‐1 with restimulation, whereas comparable levels of galectin‐1 in Th1 cells were only observed after restimulation. Co‐culturing experiments using galectin‐1^−/− and galectin‐1^+/+ Th1 and Th2 T cells demonstrated that Th2‐derived galectin‐1 induced Th1 apoptosis, whereas Th1‐derived galectin‐1 promoted Th2 cytokine production. These studies identify galectin‐1 as a cross‐regulatory cytokine that selectively antagonizes Th1 survival, while promoting TCR‐induced Th2 cytokine production.