CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones

@article{Harding1992CD28mediatedSC,
  title={CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones},
  author={Fiona A Harding and James G. Mcarthur and Jane A. Gross and David H. Raulet and James P. Allison},
  journal={Nature},
  year={1992},
  volume={356},
  pages={607-609}
}
OCCUPANCY of the T-cell antigen receptor is insufficient to induce T-cell activation optimally; a second co-stimulatory signal is required1. Exposure of T-cell clones to complexes of antigen with major histocompatibility complex molecules in the absence of the co-stimulatory signal induces a state of clonal anergy. This requirement for two stimuli for T-cell activation could have an important role in vivo in establishing peripheral tolerance to antigens not encountered in the thymus1,2. The… 
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Induction of T-cell anergy by altered T-cell-receptor ligand on live antigen-presenting cells
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A peptide analogue that is unable to stimulate clonal proliferation or production of cytokine or inositol phosphate can induce the T cells to become profoundly unresponsive to subsequent stimulation with the immunogenic peptide.
Role of co-stimulation in CD8+ T cell activation.
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The requirements for activation of naive T cells are analyzed by using splenocytes from TCR transgenic mice as a source of responding cells and it is observed that naive CD8+ T Cells are fully activated by signal 1 alone, but that co-stimulation lowers their activation threshold.
Cbl-b in T-cell activation
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The current understanding on how Cbl-b controls T- cell activation and tolerance, its in vivo implications, as well as mechanisms for tuning T-cell-mediated immune responses by this essential E3 ligase are discussed.
B7-1 Engagement of Cytotoxic T Lymphocyte Antigen 4 Inhibits T Cell Activation in the Absence of CD28
TLDR
CTLA4 can potently inhibit T cell activation in the absence of CD28, indicating that antagonism of a TCR-mediated signal is sufficient to explain the inhibitory effect of CTLA4.
Co-stimulation with 4-1BB ligand allows extended T-cell proliferation, synergizes with CD80/CD86 and can reactivate anergic T cells.
TLDR
Significantly, it is shown that T cells that had become non-responsive to anti-CD3, either alone or together with CD80/CD86 co-stimulation, and thus were anergic, could be reactivated to proliferate when costimulated with 4-1BBL,Either alone or combined with CD 80/ CD86.
B 7-1 Engagement of Cytotoxic T Lymphocyte Antigen 4 Inhibits T Cell Activation in the Absence of CD 28
TLDR
CTLA4 can potently inhibit T cell activation in the absence of CD28, indicating that antagonism of a TCR-mediated signal is sufficient to explain the inhibitory effect of CTLA4.
Multiple co-stimulatory signals are required for triggering proliferation of T cells from human secondary lymphoid tissue.
TLDR
It is found that T cells isolated from human secondary lymphoid organs (LT-T), in contrast to peripheral blood T cells (PB-T) are hyporesponsive to cross-linked anti-CD3 mAb (CD3c) even in the presence of exogenous IL-2.
B7-Mediated Co-Stimulation of T Cells: CTLA-4 Can Deliver Inhibitory Signals
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The binary view of co-stimulation via B7 should be expanded to include a third signal generated by CTLA-4 signaling, which is the delivery of a negative signal for T-cell response.
The role of the CD28 receptor during T cell responses to antigen.
TLDR
The CD28 costimulatory receptor represents a novel target for immunosuppressive drugs and induces tyrosine phosphorylation of specific substrates, including phospholipase C gamma 1, and triggers both calcium-dependent and calcium-independent signals.
Human endothelial stimulation of allogeneic T cells via a CTLA-4 independent pathway.
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