Investigation of soluble and transmembrane CTLA-4 isoforms in serum and microvesicles.
J Immunol
; 193(2): 889-900, 2014 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-24928993
ABSTRACT
Expression of the CTLA-4 gene is absolutely required for immune homeostasis, but aspects of its molecular nature remain undefined. In particular, the characterization of the soluble CTLA-4 (sCTLA-4) protein isoform generated by an alternatively spliced mRNA of CTLA4 lacking transmembrane-encoding exon 3 has been hindered by the difficulty in distinguishing it from the transmembrane isoform of CTLA-4, Tm-CTLA-4. In the current study, sCTLA-4 has been analyzed using novel mAbs and polyclonal Abs specific for its unique C-terminal amino acid sequence. We demonstrate that the sCTLA-4 protein is secreted at low levels following the activation of primary human CD4(+) T cells and is increased only rarely in the serum of autoimmune patients. Unexpectedly, during our studies aimed to define the kinetics of sCTLA-4 produced by activated human CD4(+) T cells, we discovered that Tm-CTLA-4 is associated with microvesicles produced by the activated cells. The functional roles of sCTLA-4 and microvesicle-associated Tm-CTLA-4 warrant further investigation, especially as they relate to the multiple mechanisms of action described for the more commonly studied cell-associated Tm-CTLA-4.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glicoproteínas de Membrana
/
Linfócitos T CD4-Positivos
/
Vesículas Citoplasmáticas
/
Antígeno CTLA-4
Limite:
Adult
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2014
Tipo de documento:
Article