A soluble form of CD137 (ILA/4-1BB), a member of the TNF receptor family, is released by activated lymphocytes and is detectable in sera of patients with rheumatoid arthritis

Author(s):  
Jan Michel ◽  
Joachim Langstein ◽  
Ferdinand Hofstädter ◽  
Herbert Schwarz
Gene ◽  
1995 ◽  
Vol 164 (2) ◽  
pp. 311-315 ◽  
Author(s):  
Morey Setareh ◽  
Herbert Schwarz ◽  
Martin Lotz

2021 ◽  
Vol 22 (5) ◽  
pp. 2730
Author(s):  
Jana Seidel ◽  
Sinje Leitzke ◽  
Björn Ahrens ◽  
Maria Sperrhacke ◽  
Sucharit Bhakdi ◽  
...  

Human CD137 (4-1BB), a member of the TNF receptor family, and its ligand CD137L (4-1BBL), are expressed on immune cells and tumor cells. CD137/CD137L interaction mediates bidirectional cellular responses of potential relevance in inflammatory diseases, autoimmunity and oncology. A soluble form of CD137 exists, elevated levels of which have been reported in patients with rheumatoid arthritis and various malignancies. Soluble CD137 (sCD137) is considered to represent a splice variant of CD137. In this report, however, evidence is presented that A Disintegrin and Metalloproteinase (ADAM)10 and potentially also ADAM17 are centrally involved in its generation. Release of sCD137 by transfected cell lines and primary T cells was uniformly inhibitable by ADAM10 inhibition. The shedding function of ADAM10 can be blocked through inhibition of its interaction with surface exposed phosphatidylserine (PS), and this effectively inhibited sCD137 generation. The phospholipid scramblase Anoctamin-6 (ANO6) traffics PS to the outer membrane and thus modifies ADAM10 function. Overexpression of ANO6 increased stimulated shedding, and hyperactive ANO6 led to maximal constitutive shedding of CD137. sCD137 was functionally active and augmented T cell proliferation. Our findings shed new light on the regulation of CD137/CD137L immune responses with potential impact on immunotherapeutic approaches targeting CD137.


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.


2011 ◽  
Vol 162 (5) ◽  
pp. 1186-1201 ◽  
Author(s):  
M Galuppo ◽  
G Nocentini ◽  
E Mazzon ◽  
S Ronchetti ◽  
E Esposito ◽  
...  

Immunity ◽  
2001 ◽  
Vol 15 (5) ◽  
pp. 837-846 ◽  
Author(s):  
Steven R Wiley ◽  
Linda Cassiano ◽  
Timothy Lofton ◽  
Terry Davis-Smith ◽  
Jeffrey A Winkles ◽  
...  

Neuron ◽  
2005 ◽  
Vol 45 (5) ◽  
pp. 815
Author(s):  
Jong Bae Park ◽  
Glenn Yiu ◽  
Shinjiro Kaneko ◽  
Jing Wang ◽  
Jufang Chang ◽  
...  

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)


Author(s):  
Loes A. Gravestein ◽  
Derk Amsen ◽  
Marianne Boes ◽  
Concepcion Revilla Calvo ◽  
Ada M. Kruisbeek ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document