Stat Signals Release Activated Naive Th Cells from an Anergic Checkpoint

Mohrs, Markus; Lacy, Dee A.; Locksley, Richard M.

doi:10.4049/jimmunol.170.4.1870

Cited by 19 publications

(16 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Prior studies have shown that in vitro, in the presence of Th2-polarizing conditions, STAT6KO cells cease dividing after 3 days and display a phenotype of incomplete activation (14). The same study shows that under Th1-polarizing conditions, STAT4KO cells are incompletely activated.…”

Section: Discussionsupporting

confidence: 56%

Defining Th1 and Th2 Immune Responses in a Reciprocal Cytokine Environment In Vivo

Chitnis

Salama

Grusby

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

The ability of committed Th1 and Th2 cells to function in altered cytokine environments is a central issue in autoimmune and immune-mediated diseases. Therefore, it is of interest to study the ability of Th1 or Th2 cells to expand and produce cytokine reciprocal environments in vivo. Using STAT4- and STAT6-deficient mice, we studied the expansion and cytokine production of Ag-specific Th1 or Th2 cells after transfer into Th1, Th2, or wild-type recipients. Our data show that these Th1 or Th2 cells proliferated and clonally expanded normally, regardless of the in vivo cytokine environment. These data have implications for the treatment of immune-mediated diseases by immunomodulatory agents that alter the cytokine milieu in vivo.

show abstract

Section: Discussionsupporting

confidence: 56%

Defining Th1 and Th2 Immune Responses in a Reciprocal Cytokine Environment In Vivo

Chitnis

Salama

Grusby

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Interestingly, a strong association exists between TCR ligation and expression of CIS, a negative modulator of STAT5 activity (29). Moreover, the simultaneous activation of STAT in conjunction with TCR-mediated signaling is able to allow progression of cell division and release of anergy (30). A recent study proposed a role for STAT5 in differentiation and maintenance of the IFN-␥ secreting Th1 phenotype (31).…”

Section: Discussionmentioning

confidence: 99%

Enhancer Role of STAT5 in CD2 Activation of IFN-γ Gene Expression

Gonsky

Deem

Bream

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

IFN-γ is an important immunoregulatory protein with tightly controlled expression in activated T and NK cells. Three potential STAT binding regions have been recognized within the IFN-γ promoter: 1) an IL-12-mediated STAT4 binding site at −236 bp; 2) a newly identified IL-2-induced STAT5 binding element at −3.6 kb; and 3) CD2-mediated STAT1 and STAT4 binding to an intronic element in mucosal T cells. However, functional activation of these sites remains unclear. In this study we demonstrate CD2-mediated activation of the newly characterized −3.6-kb IFN-γ STAT5 binding region. CD2 signaling of human PBMC results in activation of the −3.6-kb IFN-γ promoter, whereas mutation of the −3.6-kb STAT5 site attenuates promoter activity. Functional activation is accompanied by STAT5A but little STAT5B nucleoprotein binding to the IFN-γ STAT5 site, as determined by competition and supershift assays. STAT5 activation via CD2 occurs independent of IL-2. Western and FACS analysis shows increased phospho-STAT5 following CD2 signaling. AG490, a tyrosine kinase inhibitor affecting Jak proteins, inhibits CD2-mediated IFN-γ mRNA expression, secretion, and nucleoprotein binding to the IFN-γ STAT5 site in a dose-dependent fashion. This report is the first to describe CD2-mediated activation of STAT5 and supports STAT5 involvement in regulation of IFN-γ expression.

show abstract

“…CTLA4 is induced following T-cell receptor (TCR)/CD28 stimulation; it arrests activated Tcells, thereby keeping them in an anergic state. Arrested T-cells exit the lymph nodes and enter the circulation [19]. Blocking CTLA4 can intensify T-cell responses and exacerbate autoimmune disease [20]; CTLA4-deficient mice die by 3-4 weeks of age due to multi-organ lymphocytic infiltration and tissue destruction [17].…”

mentioning

confidence: 99%

CTLA4 gene polymorphisms are associated with chronic bronchitis

Zhu

Agustí²,

Gulsvik³

et al. 2009

European Respiratory Journal

View full text Add to dashboard Cite

Chronic obstructive pulmonary disease (COPD) is characterised by chronic and progressive dyspnoea, cough and sputum production. T-lymphocytes may play a key role in the pathogenesis of COPD and chronic bronchitis. Cytotoxic T-lymphocyte antigen (CTLA) 4 is a potential candidate gene because it modulates T-cell activation.Genetic association between nine CTLA4 single nucleotide polymorphisms (SNPs) and chronic bronchitis was assessed in 606 pedigrees (1,896 individuals) from the International COPD Genetics Network (ICGN) population. We then replicated the associations in 342 COPD subjects with chronic bronchitis and 511 COPD subjects without chronic bronchitis from Bergen, Norway. Family-based association tests were used to analyse the ICGN cohort, and a logistic regression model was used for the Bergen cohort.Six CTLA4 SNPs were significantly associated with chronic bronchitis in the ICGN cohort (0.0079fpf0.0432), with three being replicated with the same directionality of association in the Bergen cohort (0.0325fpf0.0408). One of these replicated SNPs (rs231775) encodes the Thr to Ala substitution at amino acid position 17. Haplotype analyses supported the results of single SNP analyses.Thus, CTLA4 is likely to be a genetic determinant of chronic bronchitis among COPD cases.

show abstract

Stat Signals Release Activated Naive Th Cells from an Anergic Checkpoint

Cited by 19 publications

References 61 publications

Defining Th1 and Th2 Immune Responses in a Reciprocal Cytokine Environment In Vivo

Defining Th1 and Th2 Immune Responses in a Reciprocal Cytokine Environment In Vivo

Enhancer Role of STAT5 in CD2 Activation of IFN-γ Gene Expression

CTLA4 gene polymorphisms are associated with chronic bronchitis

Contact Info

Product

Resources

About