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

• Published in: European journal of immunology Vol. 29; no. 11; pp. 3596 - 3602
• Main Authors: Magistrelli, Giovanni, Jeannin, Pascale, Herbault, Nathalie, Benoit de Coignac, Amélie, Gauchat, Jean‐François, Bonnefoy, Jean‐Yves, Delneste, Yves
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag GmbH 01.11.1999
• Subjects: Abatacept; Alternative Splicing; Amino Acid Sequence; Animals; Antigens, CD; Antigens, Differentiation - biosynthesis; Antigens, Differentiation - genetics; Base Sequence; Cells, Cultured; COS Cells; CTLA-4 Antigen; CTLA-4 protein; CTLA‐4; Gene Expression; Human T lymphocyte; Humans; Immunoconjugates; Lymphocyte Activation; Molecular Sequence Data; Recombinant Fusion Proteins - genetics; RNA, Messenger; Solubility; T-Lymphocytes - immunology; T-Lymphocytes - metabolism
• ISSN: 0014-2980; 1521-4141
• 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.