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Low concentrations of lipopolysaccharide synergize with peptides to augment human T‐cell proliferation and can prevent the induction of non‐responsiveness by CTLA4‐Ig
Author(s) -
Goodier M. R.,
Londei M.
Publication year - 2001
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2001.01147.x
Subject(s) - toxoid , antigen , stimulation , t cell , lipopolysaccharide , tumor necrosis factor alpha , immunology , in vitro , peptide , biology , immune system , microbiology and biotechnology , endocrinology , biochemistry , immunization
Summary We investigate how lipopolysaccharide (LPS) could influence antigen‐specific T‐cell responses as well as tolerance induction. Using the recall antigen tetanus toxoid for primary in vitro T‐cell stimulation, we observed that LPS synergized with peptides to augment proliferation, particularly when used at low concentrations (as little as 100 pg/ml), and that interleukin‐12 (IL‐12) was partially required for this synergistic effect. Because of the clear enhancement of in vitro peptide‐specific responses we then tested whether LPS could influence antigen‐specific tolerance driven by coincubation of antigen (tetanus toxoid; TT or immunodominant peptides) with human CTLA‐4Ig fusion protein. As expected, CTLA‐4Ig treatment inhibited responses to peptides. LPS (100 pg/ml) induced a partial recovery of primary in vitro proliferation under these conditions and the presence of LPS during the primary stimulation prevented the induction of tolerance normally observed on re‐stimulation with the same antigen alone. Contrary to the synergistic effects on peptide proliferation this action was not caused by release of IL‐12. In addition, the neutralization of tumour necrosis factor‐α (TNF‐α) during the primary stimulation did not inhibit proliferation on re‐stimulation with peptide. LPS could therefore exert dramatic effects on antigen‐specific proliferation and CTLA‐4Ig‐induced non‐responsiveness in human T cells, although via distinct mechanisms. These results reinforce the evidence that LPS influences T‐cell function, most likely as a consequence of myeloid cell activation.