scholarly journals Latency-Associated Peptide of Transforming Growth Factor β Enhances Mycobacteriocidal Immunity in the Lung duringMycobacterium bovis BCG Infection in C57BL/6 Mice

2000 ◽  
Vol 68 (11) ◽  
pp. 6505-6508 ◽  
Author(s):  
K. A. Wilkinson ◽  
T. D. Martin ◽  
S. M. Reba ◽  
H. Aung ◽  
R. W. Redline ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Growth Factor ◽  
Mrna Expression ◽  
Mycobacterium Bovis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Gamma Interferon ◽  
T Cell Proliferation

ABSTRACT Latency-associated peptide of transforming growth factor β (TGF-β) (LAP) was used to determine whether in vivo modulation of TGF-β bioactivity enhanced pulmonary immunity to Mycobacterium bovis BCG infection in C57BL/6 mice. LAP decreased BCG growth in the lung and enhanced antigen-specific T-cell proliferation and gamma interferon mRNA expression. Thus, susceptibility of the lung to primary BCG infection may be partially mediated by the immunosuppressive effects of TGF-β.

scholarly journals Defective T-Cell Activation Is Associated with Augmented Transforming Growth Factor β Sensitivity in Mice with Mutations in the Sno Gene

2003 ◽  
Vol 23 (15) ◽  
pp. 5446-5459 ◽  
Author(s):  
S. Pearson-White ◽  
M. McDuffie
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Negative Regulator ◽  
Mutant Mice ◽  
T Cell Proliferation ◽  
Receptor Ligation

ABSTRACT The proto-oncogene Sno has been shown to be a negative regulator of transforming growth factor beta (TGF-β) signaling in vitro, using overexpression and artificial reporter systems. To examine Sno function in vivo, we made two targeted deletions at the Sno locus: a 5′ deletion, with reduced Sno protein (hypomorph), and an exon 1 deletion removing half the protein coding sequence, in which Sno protein is undetectable in homozygotes (null). Homozygous Sno hypomorph and null mutant mice are viable without gross developmental defects. We found that Sno mRNA is constitutively expressed in normal thymocytes and splenic T cells, with increased expression 1 h following T-cell receptor ligation. Although thymocyte and splenic T-cell populations appeared normal in mutant mice, T-cell proliferation in response to activating stimuli was defective in both mutant strains. This defect could be reversed by incubation with either anti-TGF-β antibodies or exogenous interleukin-2 (IL-2). Together, these findings suggest that Sno-dependent suppression of TGF-β signaling is required for upregulation of growth factor production and normal T-cell proliferation following receptor ligation. Indeed, both IL-2 and IL-4 levels are reduced in response to anti-CD3ε stimulation of mutant T cells, and transfected Sno activated an IL-2 reporter system in non-T cells. Mutant mouse embryo fibroblasts also exhibited a reduced cell proliferation rate that could be reversed by administration of anti-TGF-β. Our data provide strong evidence that Sno is a significant negative regulator of antiproliferative TGF-β signaling in both T cells and other cell types in vivo.

scholarly journals Cell-Intrinsic Transforming Growth Factor-β Signaling Mediates Virus-Specific CD8+ T Cell Deletion and Viral Persistence In Vivo

Immunity ◽  
2009 ◽  
Vol 31 (1) ◽  
pp. 145-157 ◽  
Author(s):  
Roberto Tinoco ◽  
Victor Alcalde ◽  
Yating Yang ◽  
Karsten Sauer ◽  
Elina I. Zuniga
Keyword(s):  
T Cell ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Viral Persistence ◽  
Transforming Growth Factor Β ◽  
Cd8 T Cell ◽  
Cell Deletion

scholarly journals Tumor-Induced Immune Suppression of In vivo Effector T-Cell Priming Is Mediated by the B7-H1/PD-1 Axis and Transforming Growth Factor β

2008 ◽  
Vol 68 (13) ◽  
pp. 5432-5438 ◽  
Author(s):  
Shuang Wei ◽  
Andrew B. Shreiner ◽  
Nobuhiro Takeshita ◽  
Lieping Chen ◽  
Weiping Zou ◽  
...  
Keyword(s):  
T Cell ◽  
Growth Factor ◽  
Immune Suppression ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Effector T Cell ◽  
T Cell Priming

TGF-β type II receptor–deficient thymocytes develop normally but demonstrate increased CD8+ proliferation in vivo

Blood ◽  
2005 ◽  
Vol 106 (13) ◽  
pp. 4234-4240 ◽  
Author(s):  
Per Levéen ◽  
Maria Carlsén ◽  
Anna Makowska ◽  
Saemundur Oddsson ◽  
Jonas Larsson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
T Cell Development ◽  
Transforming Growth Factor Β ◽  
Cell Development ◽  
Brdu Incorporation ◽  
Inflammatory Disorder

We have taken advantage of the Cre/lox system to generate a mouse model with inducible deficiency of transforming growth factor β receptor II (TβRII). Using this approach, transforming growth factor β (TGF-β) signaling deficiency can be restricted to the hematopoietic system by bone marrow transplantation. Mice that received transplants with TβRII-/- bone marrow develop a lethal inflammatory disorder closely resembling that of TGF-β1-null mice. Previous in vitro studies have suggested multiple roles for TGF-β in T-cell development, including proliferation, apoptosis, and differentiation. We used our transplantation model to ask whether T-cell development is normal in the absence of TGF-β signaling. The findings show for the first time in vivo and in fetal thymus organ culture (FTOC) that TGF-β is not required for thymocytes to differentiate along the entire pathway of thymic T-cell development, as defined by the expression patterns of CD4, CD8, CD25, and CD44. In contrast to previous investigations, no increase of thymocyte apoptosis was observed. However, TβRII-deficient CD8+ thymocytes displayed a 2-fold increase in proliferation rate, as determined by bromodeoxyuridine (BrdU) incorporation in vivo. These results reinforce the importance of TGF-β as an immune regulator critical for T-cell function.

scholarly journals Airway epithelial cells suppress T cell proliferation by an IFNγ/STAT1/TGFβ-dependent mechanism

2012 ◽  
Vol 302 (1) ◽  
pp. L167-L173 ◽  
Author(s):  
Christine M. Deppong ◽  
Jian Xu ◽  
Steven L. Brody ◽  
Jonathan M. Green
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Epithelial Cells ◽  
Immune Responses ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Airway Epithelial Cells ◽  
T Cell Proliferation ◽  
Airway Epithelial ◽  
Specific Regulation

Organ-specific regulation of immune responses relies on the exchange of information between nonimmune and immune cells. In a primary culture model of the lung airway, we demonstrate that T cell proliferation is potently inhibited by airway epithelial cells (ECs). This is mediated by activation of the IFNγ/STAT1 pathway in the EC and transforming growth factor-β (TGFβ)-dependent suppression of T cell proliferation. In this way, the EC can restrict the expansion of T cells. Given the constant exposure of the airway to inhaled antigen, this may be important in setting a threshold for the initiation of T cell-dependent immune responses and preventing unwanted, chronic inflammation.

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