Enhanced production of TGF-β by blood monocytes from patients with active tuberculosis and presence of TGF-β in tuberculous granulomatous lung lesions

Z. Toossi, P. Gogate, H. Shiratsuchi, T. Young, J. J. Ellner

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Abstract

The expression of TGF-β, a molecule that affects both immune responsiveness and wound healing, was examined in blood monocytes and granulomatous lesions from patients with active pulmonary tuberculosis. The spontaneous release of TGF-β was higher in culture supernatants of monocytes from patients as compared with those of healthy subjects by an ELISA (p <0.0005). TGF-β activity was also confirmed in a bioassay in supernatants from patients. Next, freshly isolated monocytes from patients with tuberculosis and matched subjects were examined for TGF-β activity. Cytosmears of monocytes were stained with an Ab against TGF-β1 (anti-LC) or isotype-specific Ab by using an alkaline-phosphatase anti-alkaline phosphatase method. In contrast to monocytes from healthy individuals, 60 to 70% of monocytes from patients demonstrated cytoplasmic staining for TGF-β (n = 3). Upon hypotonic lysis, monocytes from patients with tuberculosis contained immunoreactive TGF-β (n = 3). By Northern blot analysis, monocytes from three of seven patients with tuberculosis had increased expression of TGF-β mRNA as compared with concurrently examined monocytes from healthy subjects. Within the granulomas of lung sections from two patients with untreated tuberculosis, TGF-β immunoreactivity was identified in the Langhan's giant cells mainly and to a lesser extent the epithelioid cells using anti-LC Ab and the peroxidase-anti-peroxidase technique. Thus, both blood monocytes and lung granuloma macrophages from patients with active tuberculosis express TGF-β. Excess activity of this cytokine in blood monocytes may underlie the depressed T cell responses of patients with tuberculosis. Moreover, within the infected tissues excess TGF-β activity may interfere with anti-mycobacterial mechanisms and effective granuloma formation.

Original languageEnglish (US)
Pages (from-to)465-473
Number of pages9
JournalJournal of Immunology
Volume154
Issue number1
Publication statusPublished - 1995
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

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