scholarly journals NFκB-Inducing Kinase Deficiency Results in the Development of a Subset of Regulatory T Cells, which Shows a Hyperproliferative Activity upon Glucocorticoid-Induced TNF Receptor Family-Related Gene Stimulation

2005 ◽  
Vol 175 (3) ◽  
pp. 1651-1657 ◽  
Author(s):  
Li-Fan Lu ◽  
David C. Gondek ◽  
Zachary A. Scott ◽  
Randolph J. Noelle
2005 ◽  
Vol 235 (1) ◽  
pp. 56-64 ◽  
Author(s):  
Adam P. Kohm ◽  
Joseph R. Podojil ◽  
Julie S. Williams ◽  
Jeffrey S. McMahon ◽  
Stephen D. Miller

Blood ◽  
1999 ◽  
Vol 93 (10) ◽  
pp. 3487-3493 ◽  
Author(s):  
Dan Jones ◽  
Christopher D.M. Fletcher ◽  
Karen Pulford ◽  
Aliakbar Shahsafaei ◽  
David M. Dorfman

The tumor necrosis factor (TNF) receptor family includes several important markers of activation in T cells. We examined expression patterns of two T-cell-associated members of these receptors, namely CD30 and OX40/CD134, in 148 cases of T-cell lymphoma to identify possible objective immunohistochemical criteria for subclassification of these tumors. CD30 expression was characteristic of tumors with an anaplastic (46/47 cases [98%]) or large-cell (10/21 [48%]) morphology and was seen in only scattered cells in other tumor types. In contrast, large numbers of OX40/CD134+ tumors cells were typical of angioimmunoblastic lymphoma (15/16 [94%]), angiocentric lymphoma (4/4), a subset of large-cell lymphomas (10/21 [48%]), and lymphomas with a prominent histiocytic component (6/7 [86%]). Strong OX40/CD134 and CD30 coexpression was seen in only 4% of tumors, typically those with an anaplastic/Hodgkin’s-like appearance. OX40/CD134 expression was characteristic of tumors composed of activated CD4+ T cells and was not seen in small-cell T-cell lymphomas, lymphoblastic lymphomas, or other tumor types, including B-cell lymphomas or carcinomas. These results suggest that immunostaining for OX40/CD134 may be helpful in subclassification of peripheral T-cell lymphomas and that the patterns of TNF receptor family expression in these tumors may parallel those seen within nonneoplastic helper T-cell subsets.


Blood ◽  
2005 ◽  
Vol 105 (1) ◽  
pp. 274-281 ◽  
Author(s):  
Young-June Kim ◽  
Teresa M. Stringfield ◽  
Yan Chen ◽  
Hal E. Broxmeyer

Abstract Transforming growth factor-β1 (TGF-β1), an immunosuppressive cytokine, inhibits cytotoxic T cell (CTL) immune responses. In contrast, 4-1BB (CD137), a costimulatory molecule in the tumor necrosis factor (TNF) receptor family, amplifies CTL-mediated antitumor immune responses. We investigated whether TGF-β1 responses could be reversed by 4-1BB costimulation during in vitro differentiation of naive CD8+ T cells into effector CTL cells. TGF-β1 potently suppressed CTL differentiation of human cord blood naive CD8+ T cells as determined by reduced induction of characteristic phenotypes of effector cells and cytotoxic activity. TGF-β1-mediated suppression of CTL differentiation was abrogated by 4-1BB costimulation but not by CD28 or another member in the TNF receptor family, CD30. 4-1BB costimulation suppressed Smad2 phosphorylation induced by TGF-β1, suggesting that 4-1BB effects were at the level of TGF-β1 signaling. 4-1BB effects on the TGF-β1-mediated suppression were enhanced by interleukin 12 (IL-12) but counteracted by IL-4; 4-1BB expression was up- or down-regulated, respectively, by IL-12 and IL-4. IL-4 was more dominant than IL-12 when both cytokines were present during 4-1BB costimulation in the presence of TGF-β1. This indicates critical roles for IL-4 and IL-12 in regulating 4-1BB effects on TGF-β1-mediated suppression. (Blood. 2005;105:274-281)


2010 ◽  
Vol 186 (1) ◽  
pp. 275-283 ◽  
Author(s):  
Anik L. Côté ◽  
Peisheng Zhang ◽  
Jeremy A. O'Sullivan ◽  
Valerie L. Jacobs ◽  
Carli R. Clemis ◽  
...  

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