Understanding the CD28/CTLA-4 (CD152
) pathway and its implications for costimulatory blockade.
According to the company, Cytotoxic T lymphocyte associated antigen 4 (CTLA-4), also known as CD152
, is a transmembrane protein encoded by the CTLA-4 gene that can down-regulate the activity of T cells when binding with its ligands, B7.1 and B7.2, a pathway used by tumour cells to avoid T lymphocyte attack.
Compared with the control group, the CD4+ T/CD8+ T ratio was reduced, CD154 was downregulated, CD152
was upregulated on T cell surfaces, and pro-inflammatory factors (tumor necrosis factor alpha, inducible nitric-oxide synthase, IL-1[sz]) in BV-2 cells were decreased in the experimental group.
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The cytotoxic T lymphocyte-associated molecule-4 (CTLA-4, also termed CD152
)on activated T cells connects to CD86 and CD80, and some of its inhibitory effects may be modulated by SH2-containing phosphatase (3, 4).
Ipilimumab is a human monoclonal IgG1K antibody against human CTLA-4 (CD152
), a negative regulator of T cell activity expressed on a subset of activated T cells.
Vandenberghe, "Interaction of CTLA-4 (CD152
) with CD80 or CD86 inhibits human T-cell activation," Immunology, vol.
It is a negative regulator of T-cell activation, and it is also known as CD152
. CTLA-4 is homologous to CD28 and they share the same ligands.
Suwalska et al., "CTLA-4 (CD152
) gene polymorphism at position 49 in exon 1 in Graves' disease in a Polish population of the Lower Silesian region," Archivum Immunologiae et Therapiae Experimentalis, vol.
In contrast, CTLA-4 (CD152
) is a distinct T cell receptor that, upon binding to B7 molecules, elicits an inhibitory intracellular signal .
Using this method, it is possible to produce a large amount of [CD25.sup.high][CD45RA.sup.-] active Tregs that highly express Foxp3, CTLA-4 (CD152
), and tumor necrosis factor receptor superfamily 18 (TNFRSF18).
Interaction of the cytoplasmic tail of CTLA-4 (CD152
) with a clathrin-associated protein is negatively regulated by tyrosine phosphorylation.