A human 15-kDa IFN-induced protein induces the secretion of IFN-γ

Michael Recht, Ernest C. Borden, Ernest Knight

Research output: Contribution to journalArticlepeer-review

154 Scopus citations


A 15,000 molecular weight protein (15-kDa), induced and secreted by human PBMC after treatment with IFN-α or -β, was assessed for its ability to modulate cellular function. Although it had no effect on growth or 2′5′-A synthetase activity in Daudi, U-937, or HL-60 cells, when incubated with fresh human PBMC, LPS-induced monocyte cytotoxicity against WEHI-164 target cells was augmented. This stimulation was inhibited by both an antibody against TNF-α and a rabbit polyclonal antiserum to the 15-kDa protein. Furthermore, when the 15-kDa protein was added to PBMC an increase in GTP cyclohydrolase I activity, as assessed by neopterin secretion, resulted. Neopterin secretion by PBMC in response to the 15-kDa was increased in a dose-responsive manner up to more than sixfold over baseline, with a 15-kDa concentration of less than 10 ng/ml effective. The 15-kDa protein also stimulated indoleamine 2,3-dioxygenase (IDO) activity in fresh, human PBMC. Induction of neopterin secretion and IDO activity was inhibited by a polyclonal antiserum to 15-kDa. LPS-induced cytotoxic activity was not augmented by 15-kDa pretreatment of purified monocytes, indicating the need for the presence of a second cell population and the indirect action of the 15-kDa on the induction of monocyte activities. When PBMC or purified CD3+ cells, but not purified CD14+ cells, were incubated with the 15-kDa protein, secretion of a factor was induced that resulted in the induction of IDO activity in PMA-differentiated THP-1 cells. An antibody to IFN-γ, but not IFN-α, inhibited the induction of IDO activity by this secreted factor. In addition, antiserum to the 15-kDa blocked the secretion of IFN-γ from the CD3+ cells. Thus, a 15-kDa product of IFN-α- and IFN-β-treated monocytes and lymphocytes can stimulate secretion of IFN-γ from CD3+ cells.

Original languageEnglish (US)
Pages (from-to)2617-2623
Number of pages7
JournalJournal of Immunology
Issue number8
StatePublished - Oct 15 1991
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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