Signalling via CD70, a member of the TNF family, regulates T cell functions

@article{Garca2004SignallingVC,
  title={Signalling via CD70, a member of the TNF family, regulates T cell functions},
  author={Pilar Garc{\'i}a and A Heredia and Teresa Bell{\'o}n and Emilio Carpio and Manuel Llano and Esther Caparr{\'o}s and Pedro Aparicio and Miguel L{\'o}pez-Botet},
  journal={Journal of Leukocyte Biology},
  year={2004},
  volume={76}
}
In the present work, we provide data supporting that CD70, a tumor necrosis factor (TNF)‐related molecule, defined as the CD27 ligand (CD27L), may actively regulate T cell functions similarly to other members of the TNF family (i.e., CD40L and CD30L). Cross‐linking CD70 with specific monoclonal antibodies (mAb) stimulated cytotoxicity and cytokine production in human T cell clones. Detection of intracellular‐free calcium mobilization and mitogen‐activated protein kinase phosphorylation upon mAb… 
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References

SHOWING 1-10 OF 50 REFERENCES
Engagement of CD27 with its ligand CD70 provides a second signal for T cell activation.
TLDR
It is demonstrated here that interaction of CD27 with its ligand provides a potent second signal for cytokine production, induction of activation Ags, and proliferation of unprimed CD45RA+, and to a lesser extent, of primed CD45R0+ peripheral blood T cells.
Characterization of the human CD27 ligand, a novel member of the TNF gene family.
TLDR
CD27 and its ligand are identified as potentially important structures involved in cellular interactions between T and B lymphocytes and exerted a potent inhibitory effect on the proliferation of T cells in response to allogeneic B cells and PHA.
Reverse signaling via CD30 ligand.
TLDR
Results indicate that cross-linked CD30L can transduce a signal to the ligand-bearing cell, suggesting that, as a rule, TNF family members and their cognate receptors signal bidirectionally, blurring the distinction between ligand and receptor.
Characterization of murine CD70, the ligand of the TNF receptor family member CD27.
TLDR
MCD70 transcript levels are strongly but transiently up-regulated during lymphocyte activation, which is in line with a role for the CD27-CD70 receptor pair early in the immune response, and recombinant mCD70 potently costimulates T cell proliferation.
Novel mAbs reveal potent co-stimulatory activity of murine CD27.
TLDR
Upon cross-linking, anti-CD27 mAb amplified the proliferative response of purified T lymphocytes to suboptimal stimulation with concanavalin A at least 4-fold, indicating that such mAbs can mimick ligand binding and demonstrates that CD27 also acts as a potent co-stimulatory molecule in the murine system.
Characterization of murine CD70 by molecular cloning and mAb.
TLDR
Results suggest a contribution of CD70 to murine T-B cognate interaction as proposed in the human system, and generate cDNA transfectants and anti-mCD70 mAb (FR70), which inhibited binding of a murine CD27-Fc fusion protein to mCD70 transfectant.
Expression of the Murine CD27 Ligand CD70 In Vitro and In Vivo4
The interaction between TNFR family member CD27 and its ligand CD70 promotes lymphocyte expansion and effector cell formation. In humans, control of CD27 function is partly regulated by the
Aberrant expression and reverse signalling of CD70 on malignant B cells
TLDR
In a subset of malignant B cells CD70 can operate as receptor and as such might contribute to progression of these B‐cell malignancies.
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