title: A dimeric form of soluble recombinant sheep LFA-3(CD58) inhibits human T-cell proliferation by generating regulatory T cells.
abstract: We recently observed that the soluble recombinant from of sheep LFA-3, termed sLFA-3 is biologically active as determined by E-rosette inhibition and inhibition of human T-cell proliferation in response to the recall antigen. In the present study, we examined the immunosuppressive properties of a derivative of sLFA-3, a dimeric form of the first domain (D1) of sLFA-3, named sD1Hcys dimer which was made by oxidative binding 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 sD1Hcys dimer, we obtained evidence that antigen-stimulated T-cell proliferation was inhibited by the suppressor T cell, mainly CD4 + CD45RA - CD45RO + and CD8 + CD45RA - CD45RO + T cells, generated by incubating PBLs with a low dose (0.5 microgram/ml) of sD1Hcys dimer in the presence of a low dose of IL-2 and GM-CSF. Flow cytometric analysis showed that the expression of some surface molecules on T cells were modulated by a high dose (5 micrograms/ml) of sD1Hcys dimer such as downregulation of CD3 and upregulation of IL-2R, but were not modulated by a low dose (0.5 microgram/ml) of the sD1Hcys dimer. These findings suggest that the sD1Hcys dimer exerts its suppressive effects on the antigen-induced proliferation assay by generating suppressor T cells. The sD1Hcys dimer might therefore have potential as an immunotherapeutic agent to inhibit and/or anergize antigen-specific T-cell responses.
authors.affiliation: Kaneka Corporation, Takasago Research Laboratories, Research Institute, Hyogo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yamashita
authors.forename: T
authors.initials: T
authors.lastname: Kakutani
authors.forename: T
authors.initials: T
authors.lastname: Ohashi
authors.forename: T
authors.initials: T
authors.lastname: Saibara
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D018968:CD58 Antigens / Q000378:metabolism / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D019281:Dimerization; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D017493:Leukocyte Common Antigens / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects*; D016131:Lymphocyte Subsets; D010084:Oxidation-Reduction; D011994:Recombinant Proteins / Q000494:pharmacology; D012756:Sheep; D012995:Solubility; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000502:physiology*
chemical_list: D018968:CD58 Antigens; D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D017493:Leukocyte Common Antigens