CTLA-4 and its Role in Immune Homeostasis

Cytotoxic T lymphocyte associated gene-4 (CTLA-4), also known as CD152, is a type I glycoprotein that belongs to the immunoglobulin superfamily. CTLA-4 is required for immune homeostasis as it functions as a checkpoint for T-cell activation and a critical inhibitor of autoimmunity. CTLA-4 is constitutively expressed in Foxp3+ regulatory T cells, where it mediates cell extrinsic control of effector responses to regulate immune suppression. In contrast, CTLA-4 expression is only induced in T cells following activation, where CLTA-4 primarily acts as a co-inhibitory molecule to transmit a negative feedback signal. CLTA-4 counteracts with the B7:CD28 pathway by binding to the B7 ligand on antigen-presenting cells with a higher affinity to antagonise CD28 positive co-stimulatory signalling. CTLA4 any also function by downregulating ligand expression and transmitting inhibitory signals.

The membrane bound CTLA-4, mCTLA-4, contains an extracellular V domain, a transmembrane domain and a cytoplasmic tail. An alternatively spliced isoform has also been identified to be a secreted soluble form, sCTLA-4, which lacks the transmembrane domain and possess a different cytoplasmic tail. sCTLA-4 can still bind B7 and modulate the strength and durability of the B7:CD28-mediated costimulation. However, sCTLA-4 may also interfere with B7:mCTLA-4 interactions, causing a reduction in the negative signal. sCTLA-4 also exhibits a dual effect on cytokine production to modulate T cell proliferation.  sCTLA4 can inhibit the secretion of activator cytokines IFN-γ , IL-2, IL-7, and IL-13 and activate the secretion of TGF-β and IL-10.

The levels of sCTLA-4 play a role in determining the fate of immune responses. Low levels of sCTLA-4 have been detected in normal human serum. Increased levels of sCTLA-4 have been observed in several autoimmune diseases such as Graves' disease, type 1 diabetes, celiac disease, Crohn’s disease, systemic lupus erythematosus, and systemic sclerosis. Understanding the role of sCTLA-4 in modulating the immune response may provide an insight to its relevance in autoimmune disease pathogenesis.

Monoclonal Antibodies:

Anti-sCTLA-4 antibody CRB4B8 (crb5005104)

Anti-sCTLA-4 antibody CRB10D1  (crb5005105)

Polyclonal Antibodies:

Anti-sCTLA-4 antibody 4017 (crb2005177)

Anti-sCTLA-4 antibody 4018 (crb2005178)

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