IL-21 promotes T lymphocyte survival by activating the phosphatidylinositol-3 kinase signaling cascade

Ostiguy, Valérie; Allard, Ève-Line; Marquis, Miriam; Leignadier, Julie; Labrecque, Nathalie

doi:10.1189/jlb.0806494

Cited by 67 publications

(80 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our report is the first to show that resting Vg9/Vd2 T cells express IL-21R on their surface, and that the expression of IL-21R is greatly enhanced upon stimulation. Binding of IL-21 to gd T cells had so far only been described in mice [39]. Our findings imply that resting Vg9/Vd2 T cells are directly responsive to IL-21 in the microenvironment, and even more so shortly after activation with HMB-PP.…”

mentioning

confidence: 52%

IL‐21 enhances the potential of human γδ T cells to provide B‐cell help

et al. 2011

View full text Add to dashboard Cite

Vc9/Vd2 T cells are a minor subset of T cells in human blood and differ from all other lymphocytes by their specific responsiveness to (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), a metabolite produced by a large range of microbial pathogens. Vc9/Vd2 T cells can be skewed towards distinct effector functions, in analogy to, and beyond, the emerging plasticity of CD4 1 T cells. As such, depending on the microenvironment, Vc9/Vd2 T cells can assume features reminiscent of Th1, Th2, Th17 and Treg cells as well as professional APCs. We here demonstrate that Vc9/Vd2 T cells express markers associated with follicular B helper T (T FH ) cells when stimulated with HMB-PP in the presence of IL-21. HMB-PP induces upregulation of IL-21R on Vc9/Vd2 T cells. In return, IL-21 plays a co-stimulatory role in the expression of the B-cell-attracting chemokine CXCL13, the CXCL13 receptor CXCR5 and the inducible co-stimulator by activated Vc9/Vd2 T cells, and enhances their potential to support antibody production by B cells. The interaction between HMB-PP-responsive Vc9/Vd2 T cells, IL-21-producing T FH cells and B cells in secondary lymphoid tissues is likely to impact on the generation of high affinity, class-switched antibodies in microbial infections. Key words: Bacterial infections . B cells . cd T cells . IL-21 . T FH cells IntroductionThe establishment of long-term humoral immunity depends on the production of high-affinity antibodies capable of neutralising and opsonising invading pathogens. These antibodies are generated through somatic hypermutation, class switch recombination and affinity maturation of activated B cells, processes that take place in the germinal centres (GCs) of secondary lymphoid organs and depend on cognate help provided by CD4 1 follicular B helper T (T FH ) cells [1,2]. Human T FH cells are defined by the expression of characteristic markers [3][4][5][6][7]: the transcriptional repressor Bcl-6 that directs T FH lineage commitment; the chemokine receptor CXCR5 that enables T FH cells to migrate into the B-cell follicles; the CXCR5 ligand CXCL13 that attracts further CXCR5 1 cells such as naïve B cells and early activated CD4 1 T cells; the co-stimulatory molecules, inducible co-stimulator (ICOS) and programmed cell death 1 (PD-1), which interact with their corresponding ligands on B cells; and the cytokine IL-21 that steers B-cell differentiation and antibody production. Murine T FH cells express the same panel of markers with the exception of CXCL13.While the crucial role of T FH cells in providing B-cell help is undisputed, other T-cell subsets including CD8 1 T cells, NKT cells and gd T cells contribute to the outcome of humoral immune responses [8][9][10]. gd T cells support antibody production in immunised and infected mice [11][12][13] 110 [17,18], where they are scattered throughout the T zone and clustered within GCs [8]. Early studies in lupus patients led to the isolation of human gd T-cell lines capable of inducing autoantibody production by autologous B cells [19]. Subsequent ...

show abstract

mentioning

confidence: 52%

IL‐21 enhances the potential of human γδ T cells to provide B‐cell help

et al. 2011

View full text Add to dashboard Cite

show abstract

“…1A). Compared with freshly isolated cells, P14 cells incubated with IL-21 alone showed markedly decreased proliferation, probably because IL-21 at the concentration used in this study is less efficient than IL-7 or IL-15 in providing survival signals to naive CD8 T cells (23). In contrast, cells primed with the synergistic combination of IL-21 and IL-7 or IL-15 displayed robust proliferation to L6F, A4Y, and W4Y to which naive P14 cells showed weak to moderate responses (Fig.…”

Section: Resultsmentioning

confidence: 77%

Exposure to IL-15 and IL-21 Enables Autoreactive CD8 T Cells To Respond to Weak Antigens and Cause Disease in a Mouse Model of Autoimmune Diabetes

Ramanathan

Dubois

Chen

et al. 2011

The Journal of Immunology

View full text Add to dashboard Cite

Autoreactive CD8+ T lymphocytes play a key role in the pathogenesis of several autoimmune diseases. It is not yet well understood how autoreactive CD8+ T cells, which express TCRs with low reactivity toward self-Ags, gain the ability to respond to autoantigens to cause disease. Previously, we have shown that prior stimulation of CD8+ T cells with synergistic combinations of cytokines produced by the innate immune response, such as IL-21 and IL-15, induces Ag-independent proliferation. Such “cytokine-primed” CD8 T cells displayed increased responsiveness to limiting quantities of the cognate Ag. In this paper, we report that prior stimulation with IL-15 and IL-21 also enables CD8+ T cells to respond to weakly agonistic TCR ligands, resulting in proliferation, cytokine secretion, and cytolytic activity. Using a transgenic mouse model of autoimmune diabetes, we show that cytokine-primed autoreactive CD8+ T cells induce disease following stimulation by weak TCR ligands, but their diabetogenic potential is dependent on continuous availability of IL-15 in vivo. These findings suggest that inflammatory cytokines could facilitate the triggering of autoreactive CD8+ T cells by weak autoantigens, and this mechanism may have important implications for autoimmune diseases associated with microbial infections and chronic inflammation.

show abstract

“…characteristics [13]. Moreover, co-stimulation controlled by IL-21 is necessary for high level expression of CXCR5, which is required for migration into GCs [42,43]. Another important transcription factor [14].…”

Section: The Intensity Of Focus Scores In Association With T Fh Cellsmentioning

confidence: 99%

Follicular helper T cells may play an important role in the severity of primary Sjögren's syndrome

Szabó

Papp

Baráth

et al. 2013

Clinical Immunology

141

View full text Add to dashboard Cite

show abstract

IL-21 promotes T lymphocyte survival by activating the phosphatidylinositol-3 kinase signaling cascade

Cited by 67 publications

References 85 publications

IL‐21 enhances the potential of human γδ T cells to provide B‐cell help

IL‐21 enhances the potential of human γδ T cells to provide B‐cell help

Exposure to IL-15 and IL-21 Enables Autoreactive CD8 T Cells To Respond to Weak Antigens and Cause Disease in a Mouse Model of Autoimmune Diabetes

Follicular helper T cells may play an important role in the severity of primary Sjögren's syndrome

Contact Info

Product

Resources

About