Differential activation of signal transducer and activator of transcription (STAT)3 and STAT5 and induction of suppressors of cytokine signalling in Th1 and Th2 cells

Abstract

Cytokines direct the differentiation of naive CD4⁺ T cells into either IFN‐γ‐producing T_h1 cells or IL‐4‐producing T_h2 cells. In this study, we analyzed the activation of signal transducer and activator of transcription (STAT)1, STAT3 and STAT5 (together with STAT4 and STAT6), and the expression of the recently identified suppressor of cytokine signalling (SOCS) proteins, in differentiated T_h1 and T_h2 cells, both before and after re‐stimulation with anti‐CD3 and anti‐CD28. In addition to the polarized activation of STAT4 in T_h1 cells and STAT6 in T_h2 cells, we found that STAT3 and STAT5 are selectively activated in T_h1 cells after differentiation. This activation of STAT3 and STAT5 was maintained after TCR re‐stimulation. The selective activation of STAT3 and STAT5 in T_h1 cells was associated with differential induction of SOCS molecules. After re‐stimulation, SOCS1 expression was significantly increased in T_h2 cells, but not in T_h1 and non‐polarized ‘T_h’ cells. Additionally, the level of CIS was higher in T_h2 cells compared with T_h1 and T_h cells. In contrast, the expression of SOCS3 was higher in T_h1 cells. The differential induction of SOCS proteins was paralleled by the differential expression of cytokines in re‐stimulated T_h1 and T_h2 cells (IFN‐γ and IL‐4/IL‐13 respectively). Our results suggests that STAT3 and STAT5, possibly regulated by the SOCS proteins, may play a role in the differentiation of T_h cells, and in the maintenance of the T_h1 and T_h2 phenotype.