Suppression of lymphocyte responses by tuberculous plasma and mycobacterial arabinogalactan. Monocyte dependence and indomethacin reversibility

M. E. Kleinhenz, J. J. Ellner, P. J. Spagnuolo, T. M. Daniel

Research output: Contribution to journalArticle

Abstract

During tuberculosis, exposure of monocytes to circulating factors may induce the suppressor activity observed in some anergic patients. To explore this possibility, we examined the effects of plasma pooled from 28 untreated tuberculosis (TB) patients and the mycobacterial cell wall polysaccharide D-arabino-D-galactan (AG) on the in vitro function of peripheral blood mononuclear cells (PBMC) from healthy donors. In the [3H]thymidine incorporation assay, stimulated responses of PBMC incubated in culture medium supplemented with TB plasma or co-cultured with 3.0 μg/ml AG were depressed significantly when compared with control responses. Cytotoxicity and altered kinetics of stimulated DNA synthesis did not contribute to the observed suppression, TB plasma and AG-induced suppression of the PBMC response to purified protein derivative was monocyte dependent and indomethacin reversible. In addition, TB plasma and AG directly inhibited the phytohemagglutinin-stimulated responses of T lymphocytes. In a quantitative assay of monocyte attachment to plastic, both TB plasma and AG significantly increased monocyte adherence from basal levels. These effects on monocyte adherence were reversed with indomethacin or antibody to mycobacterial polysaccharide. In addition, TB plasma passed over an immunoabsorbent column of Sepharose-linked antibody to mycobacterial polysaccharide was depleted of the suppressive and monocyte-adherence augmenting factors. 3.0 μg/ml Ag stimulated a fivefold increase in prostaglandin E2 production by cultured mononuclear cells. Our data suggest that AG circulating alone or bound in immune complexes may account for the observed effects of TB plasma. Similar in vivo exposure may contribute to the cell-mediated suppression of lymphocyte responses in tuberculosis.

Original languageEnglish (US)
Pages (from-to)153-162
Number of pages10
JournalJournal of Clinical Investigation
Volume68
Issue number1
StatePublished - 1981
Externally publishedYes

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Indomethacin
Monocytes
Tuberculosis
Lymphocytes
Polysaccharides
Blood Cells
arabinogalactan
Antibodies
Phytohemagglutinins
Antigen-Antibody Complex
Dinoprostone
Sepharose
Thymidine
Cell Wall
Plastics
Culture Media
galactan F
Cultured Cells
Tissue Donors
T-Lymphocytes

ASJC Scopus subject areas

  • Medicine(all)

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Suppression of lymphocyte responses by tuberculous plasma and mycobacterial arabinogalactan. Monocyte dependence and indomethacin reversibility. / Kleinhenz, M. E.; Ellner, J. J.; Spagnuolo, P. J.; Daniel, T. M.

In: Journal of Clinical Investigation, Vol. 68, No. 1, 1981, p. 153-162.

Research output: Contribution to journalArticle

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