Human Soluble CD80 is generated by alternative splicing, and recombinant soluble CD80 binds to CD28 and CD152 influencing T-cell activation.
CD80 is a costimulatory factor mainly expressed on the surface of activated monocytes, B cells and dendritic cells. In this study, we demonstrate that 24% of healthy individuals have soluble forms of CD80, sCD80, in their serum. The concentration of sCD80 ranged from 0 to 1 mg/l. At the mRNA level, we detected a spliced form s1CD80 (771 bp), in unstimulated monocytes and B cells, while another form named s2CD80 (489 bp) was expressed in activated T cells as well as in freshly isolated and activated monocytes. s1CD80 lacks the transmembrane domain, and the IgC-like domain plus the transmembrane domain are spliced out of s2CD80. We also present data demonstrating that recombinant s1CD80 binds to recombinant CD152-Ig and CD28-Ig. It can also bind to T cells, preferentially to activated T cells. Recombinant sCD80 had immunomodulatory effects shown by its inhibition of the mixed lymphocyte reaction and inhibition of T-cell proliferation. sCD80 in human serum adds a new member to the family of soluble receptors, implying a network of soluble costimulatory factors with functional relevance. The inhibitory effect of the recombinant protein on T-cell activation makes it a possible candidate for treatment of diseases associated with hyperactivated T cells.
Kakoulidou
M
M
Immunological Research Unit, Department of Medicine, Center for Molecular Medicine L8: 00, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden.
Giscombe
R
R
Zhao
X
X
Lefvert
A K
AK
Wang
X
X
D017398:Alternative Splicing; D015703:Antigens, CD / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000378:metabolism*; D018122:B7-1 Antigen / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D015153:Blotting, Western; D018106:CD28 Antigens / Q000378:metabolism*; D060908:CTLA-4 Antigen; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D020033:Protein Isoforms; D012333:RNA, Messenger; D011994:Recombinant Proteins