Related Experiment Video
Updated: May 5, 2026

Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes
Published on: September 27, 2013
IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells
Thomas Korn1, Estelle Bettelli1, Wenda Gao2
1Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Abstract:
On activation, naive T cells differentiate into effector T-cell subsets with specific cytokine phenotypes and specialized effector functions. Recently a subset of T cells, distinct from T helper (T(H))1 and T(H)2 cells, producing interleukin (IL)-17 (T(H)17) was defined and seems to have a crucial role in mediating autoimmunity and inducing tissue inflammation. We and others have shown that transforming growth factor (TGF)-beta and IL-6 together induce the differentiation of T(H)17 cells, in which IL-6 has a pivotal function in dictating whether T cells differentiate into Foxp3+ regulatory T cells (T(reg) cells) or T(H)17 cells. Whereas TGF-beta induces Foxp3 and generates T(reg) cells, IL-6 inhibits the generation of T(reg) cells and induces the production of IL-17, suggesting a reciprocal developmental pathway for T(H)17 and T(reg) cells. Here we show that IL-6-deficient (Il6-/-) mice do not develop a T(H)17 response and their peripheral repertoire is dominated by Foxp3+ T(reg) cells. However, deletion of T(reg) cells leads to the reappearance of T(H)17 cells in Il6-/- mice, suggesting an additional pathway by which T(H)17 cells might be generated in vivo. We show that an IL-2 cytokine family member, IL-21, cooperates with TGF-beta to induce T(H)17 cells in naive Il6-/- T cells and that IL-21-receptor-deficient T cells are defective in generating a T(H)17 response.
Related Concept Videos
Cell-mediated Immune Responses
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...
Cells of the Adaptive Immune Response
T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...
T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
B Cell Activation and Differentiation
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...

