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 microgram/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 microgram/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.