A DIMERIC FORM OF SOLUBLE RECOMBINANT SHEEP LFA-3(CD58) INHIBITS HUMAN T-CELL PROLIFERATION BY GENERATING REGULATORY T-CELLS

We recently observed that the soluble recombinant form of sheep LFA-3, termed sLFA-3 is biologically active as determined by E-rosette inhib ition and inhibition of human T-cell proliferation in response to the recall antigen. In the present study, we examined the immunosuppressiv e properties of a derivative of sLFA-3, a dimeric form of the first do main (D1) of sLFA-3, named sD1Hcys dimer which was made by oxidative b inding of the two D1 molecules through disulfide bonds formed between the SH side chains of a cysteine which was added to the C-terminal of the D1 domain. By investigating the suppressive properties of the sD1H cys dimer, we obtained evidence that antigen-stimulated T-cell prolife ration was inhibited by the suppressor T cell, mainly CD4 + CD45RA - C D45RO + and CD8 + CD45RA - CD45RO + T cells, generated by incubating P BLs with a low dose (0.5 mu g/ml) of sD1Hcys dimer in the presence of a low dose of IL-2 and GM-CSF. Flow cytometric analysis showed that th e expression of some surface molecules on T cells were modulated by a high dose (5 mu g/ml) of sD1Hcys dimer such as downregulation of CD3 a nd upregulation of IL-2R, but were not modulated by a low dose (0.5 mu g/ml) of the sD1Hcys dimer. These findings suggest that the sD1Hcys d imer exerts its suppressive effects on the antigen-induced proliferati on assay by generating suppressor T cells. The sD1Hcys dimer might the refore have potential as an immunotherapeutic agent to inhibit and/or anergize antigen-specific T-cell responses. (C) 1997 Elsevier Science B.V.