A soluble form of CTLA-4 generated by alternative splicing is expressed by nonstimulated human T cells

Eur J Immunol. 1999 Nov;29(11):3596-602. doi: 10.1002/(SICI)1521-4141(199911)29:11<3596::AID-IMMU3596>3.0.CO;2-Y.


CTLA-4, expressed by activated T cells, transduces an inhibitory signal. We show here that PCR amplification of the coding sequence of CTLA-4 in nonstimulated human T lymphocytes results in the amplification of two transcripts of 650 and 550 bp. Sequencing shows that the larger form codes for membrane CTLA-4 and the 550-bp transcript is a spliced variant in which exon 2 coding for the transmembrane region is deleted. This spliced cDNA has been named CTLA-4delTM. The splicing induces a frame shift which results in the addition of 22 extra amino acids before a translational termination. Activation of T cells with phorbol 12-myristate 13-acetate plus ionomycin or anti-CD3 plus anti-CD28 monoclonal antibodies induces a suppression of CTLA-4delTM mRNA expression associated with a preferential expression of the membrane CTLA-4 mRNA, showing that CTLA-4delTM mRNA expression is restricted to nonactivated T cells. A soluble immunoreactive form of CTLA-4 was detected in the serum of 14 / 64 healthy subjects. These results suggest that nonstimulated T cells may constitutively produce a soluble form of CTLA-4 which may have an important role in the regulation of immune homeostasis.

MeSH terms

  • Abatacept
  • Alternative Splicing*
  • Amino Acid Sequence
  • Animals
  • Antigens, CD
  • Antigens, Differentiation / biosynthesis*
  • Antigens, Differentiation / genetics
  • Base Sequence
  • COS Cells
  • CTLA-4 Antigen
  • Cells, Cultured
  • Gene Expression
  • Humans
  • Immunoconjugates*
  • Lymphocyte Activation
  • Molecular Sequence Data
  • RNA, Messenger
  • Recombinant Fusion Proteins / genetics
  • Solubility
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*


  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Immunoconjugates
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Abatacept