scholarly journals Transforming Growth Factor-β Protein Inversely Regulates in Vivo Differentiation of Interleukin-17 (IL-17)-producing CD4+ and CD8+ T Cells

2011 ◽  
Vol 287 (5) ◽  
pp. 2943-2947 ◽  
Author(s):  
Ved Prakash Dwivedi ◽  
Sultan Tousif ◽  
Debapriya Bhattacharya ◽  
Durbaka Vijay Raghva Prasad ◽  
Luc Van Kaer ◽  
...  
Keyword(s):  
T Cells ◽  
Growth Factor ◽  
Cd8 T Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 17 ◽  
Β Protein ◽  
In Vivo Differentiation

scholarly journals Transforming Growth Factor β and Immunosuppression in Experimental Visceral Leishmaniasis

1998 ◽  
Vol 66 (3) ◽  
pp. 1233-1236 ◽  
Author(s):  
Virmondes Rodrigues ◽  
João Santana da Silva ◽  
Antonio Campos-Neto
Keyword(s):  
T Cells ◽  
Growth Factor ◽  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Spleen Cells ◽  
Immunohistochemical Studies

ABSTRACT Hamsters infected with Leishmania donovani develop a disease similar to human kala-azar. They present hypergammaglobulinemia, and their T cells do not respond to parasite antigens. This unresponsiveness has been primarily ascribed to defects in antigen-presenting cells (APCs), because these cells are unable to stimulate proliferation of parasite-specific T cells from immunized animals. In this study, we show that APCs (adherent spleen cells) fromL. donovani-infected hamsters produce high levels of the inhibitory cytokine transforming growth factor β (TGF-β). Immunohistochemical studies with an anti-TGF-β monoclonal antibody (MAb) showed that this cytokine is abundantly produced in vivo by the spleen cells of infected animals. In addition, high levels of TGF-β are produced in vitro by infected hamster cells, either spontaneously or after stimulation with parasite antigen or lipopolysaccharide. Furthermore, in vivo-infected adherent cells obtained from spleens ofL. donovani-infected hamsters caused profound inhibition of the in vitro antigen-induced proliferative response of lymph node cells from hamsters immunized with leishmanial antigens. Moreover, this inhibition was totally abrogated by the anti-TGF-β MAb. These results suggest that the immunosuppression observed in visceral leishmaniasis is, at least in part, due to the abundant production of TGF-β during the course of the infection.

Calcineurin-dependent negative regulation of CD94/NKG2A expression on naive CD8+ T cells

Blood ◽  
2011 ◽  
Vol 118 (1) ◽  
pp. 116-128 ◽  
Author(s):  
Jae-Ho Cho ◽  
Hee-Ok Kim ◽  
Kylie Webster ◽  
Mainthan Palendira ◽  
Bumsuk Hahm ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Chronic Infections ◽  
Nk Receptors ◽  
Variable Expression ◽  
Dependent Inhibition

Abstract Immune responses lead to expression of immunoregulatory molecules on T cells, including natural killer (NK) receptors, such as CD94/NKG2A on CD8+ T cells; these receptors restrain CD8+ responses, thereby preventing T-cell exhaustion in chronic infections and limiting immunopathology. Here, we examined the requirements for inducing CD94/NKG2A on T cells responding to antigen. In vitro, moderate induction of CD94/NKG2A expression occurred after exposure of naive CD8+ (but not CD4+) cells to CD3 ligation or specific peptide. Surprisingly, expression was inhibited by CD28/B7 costimulation. Such inhibition applied only to CD94/NKG2A and not other NK receptors (NKG2D) and was mediated by IL-2. Inhibition by IL-2 occurred via a NFAT cell-independent component of the calcineurin pathway, and CD94/NKG2A induction was markedly enhanced in the presence of calcineurin blockers, such as FK506 or using calcineurin-deficient T cells, both in vitro and in vivo. In addition to CD28-dependent inhibition by IL-2, CD94/NKG2A expression was impaired by several other cytokines (IL-4, IL-23, and transforming growth factor-β) but enhanced by others (IL-6, IL-10, and IL-21). The complex interplay between these various stimuli may account for the variable expression of CD94/NKG2A during responses to different pathogens in vivo.

scholarly journals CD8 Co-receptor promotes susceptibility of CD8+ T cells to transforming growth factor-β (TGF-β)-mediated suppression

2010 ◽  
Vol 60 (2) ◽  
pp. 291-297 ◽  
Author(s):  
Andrew Zloza ◽  
Michael C. Jagoda ◽  
Gretchen E. Lyons ◽  
Michael C. Graves ◽  
Frederick J. Kohlhapp ◽  
...  
Keyword(s):  
T Cells ◽  
Growth Factor ◽  
Cd8 T Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β

scholarly journals Blockade of transforming growth factor-β signaling in tumor-reactive CD8+ T cells activates the antitumor immune response cycle

2006 ◽  
Vol 5 (7) ◽  
pp. 1733-1743 ◽  
Author(s):  
Qiang Zhang ◽  
Ximing J. Yang ◽  
Shilajit D. Kundu ◽  
Michael Pins ◽  
Borko Javonovic ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Growth Factor ◽  
Cd8 T Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Antitumor Immune Response

scholarly journals Generation and function of immunosuppressive human and murine CD8+ T cells by transforming growth factor-β and retinoic acid

Immunology ◽  
2011 ◽  
Vol 134 (1) ◽  
pp. 82-92 ◽  
Author(s):  
Diana Fleissner ◽  
Annika Frede ◽  
Markus Knott ◽  
Torben Knuschke ◽  
Robert Geffers ◽  
...  
Keyword(s):  
T Cells ◽  
Retinoic Acid ◽  
Growth Factor ◽  
Cd8 T Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
And Function

Mesenchymal stromal cells cross-present soluble exogenous antigens as part of their antigen-presenting cell properties

Blood ◽  
2009 ◽  
Vol 114 (13) ◽  
pp. 2632-2638 ◽  
Author(s):  
Moïra François ◽  
Raphaëlle Romieu-Mourez ◽  
Sophie Stock-Martineau ◽  
Marie-Noëlle Boivin ◽  
Jonathan L. Bramson ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Stromal Cells ◽  
Antigen Processing ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Cross Presentation ◽  
Ifn Γ

Abstract Recent studies involving bone marrow mesenchymal stromal cells (MSCs) demonstrated that interferon (IFN)–γ stimulation induces major histocompatibility complex (MHC) class II–mediated antigen presentation in MSCs both in vitro and in vivo. Concordantly, we investigated the ability of MSCs to present extracellular antigen through their MHC class I molecules, a process known as cross-presentation. Using an in vitro antigen presentation assay, we demonstrated that murine MSCs can cross-present soluble ovalbumin (OVA) to naive CD8+ T cells from OT-I mice. Cross-presentation by MSC was proteasome dependent and partly dependent on transporter associated with antigen-processing molecules. Pretreatment of MSC with IFN-γ increased cross-presentation by up-regulating antigen processing and presentation. However, although the transcription of the transporter associated with antigen processing-1 molecules and the immunoproteasome subunit LMP2 induced by IFN-γ was inhibited by transforming growth factor-β, the overall cross-presentation capacity of MSCs remained unchanged after transforming growth factor-β treatment. These observations were validated in vivo by performing an immune reconstitution assay in β2-microglobulin−/− mice and show that OVA cross-presentation by MSCs induces the proliferation of naive OVA-specific CD8+ T cells. In conclusion, we demonstrate that MSCs can cross-present exogenous antigen and induce an effective CD8+ T-cell immune response, a property that could be exploited as a therapeutic cell-based immune biopharmaceutic for the treatment of cancer or infectious diseases.

Transforming Growth Factor–β Signaling in T Cells Promotes Stabilization of Atherosclerotic Plaques Through an Interleukin-17–Dependent Pathway

2013 ◽  
Vol 5 (196) ◽  
pp. 196ra100-196ra100 ◽  
Author(s):  
Anton Gisterå ◽  
Anna-Karin L. Robertson ◽  
John Andersson ◽  
Daniel F. J. Ketelhuth ◽  
Olga Ovchinnikova ◽  
...  
Keyword(s):  
T Cells ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Transforming Growth Factor Β ◽  
Atherosclerotic Plaques ◽  
Interleukin 17 ◽  
Type I ◽  
T Helper 17

Adaptive immunity has a major impact on atherosclerosis, with pro- and anti-atherosclerotic effects exerted by different subpopulations of T cells. Transforming growth factor–β (TGF-β) may promote development either of anti-atherosclerotic regulatory T cells or of T helper 17 (TH17) cells, depending on factors in the local milieu. We have addressed the effect on atherosclerosis of enhanced TGF-β signaling in T cells. Bone marrow from mice with a T cell–specific deletion ofSmad7, a potent inhibitor of TGF-β signaling, was transplanted into hypercholesterolemicLdlr−/−mice.Smad7-deficient mice had significantly larger atherosclerotic lesions that contained large collagen-rich caps, consistent with a more stable phenotype. The inflammatory cytokine interleukin-6 (IL-6) was expressed in the atherosclerotic aorta, and increased mRNA for IL-17A and the TH17-specific transcription factor RORγt were detected in draining lymph nodes. TreatingSmad7-deficient chimeras with neutralizing IL-17A antibodies reversed stable cap formation. IL-17A stimulated collagen production by human vascular smooth muscle cells, and RORγt mRNA correlated positively with collagen type I and α-smooth muscle actin mRNA in a biobank of human atherosclerotic plaques. These data link IL-17A to induction of a stable plaque phenotype, could lead to new plaque-stabilizing therapies, and should prompt an evaluation of cardiovascular events in patients treated with IL-17 receptor blockade.

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