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 belonging to the immunoglobulin superfamily. CTLA-4 is required for immune homeostasis because it functions as a checkpoint for T-cell activation and is 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 down-regulating 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, Coeliac 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.

Antibodies against the soluble CTLA-4 isoform are now available to order from our Discovery® catalogue:

Rabbit Polyclonal anti-sCTLA-4

 4017 anti-human (catalogue number: crb2005177)

4018 anti-human (catalogue number: crb2005178)

Mouse Monoclonal anti-sCTLA-4

CRB4B8 anti-human (catalogue number: crb5005104)

 CRB10D1 anti-human (catalogue number: crb5005105)

Antibodies were designed and manufactured by Cambridge Research Biochemicals in the United Kingdom. For more information see:

Wicker et al. (2015). Journal of Immunology. 193:889-900. PMID: 24928993

Case Study: Analysis of the molecular nature of CTLA-4 using custom Monoclonal and Polyclonal Antibodies

Leave a Reply