Modulation of pokeweed-mitogen-induced immunoglobulin secretion by human bronchoalveolar cells.

The effects of human bronchoalveolar cells on pokeweed-mitogen-induced immunoglobulin(Ig) secretion in vitro were investigated, using a reverse hemolytic plaque assay. Unfractionated peripheral blood mononuclear cells from 7 nonsmoking normal subjects responded to pokeweed mitogen with a geometric mean of 6,550 Ig-secreting cells per million cultured mononuclear cells, whereas monocyte-depleted mononuclear cells responded with only 148 (p = 0.015, paired 2-tailed t test). The addition of 1 to 20% autologous bronchoalveolar cells to unfractionated mononuclear cells progressively suppressed the Ig-secretory response (p less than 0.01, paired t test comparing 0 to greater than or equal to 10% added bronchoalveolar cells). However, the addition of low concentrations of bronchoalveolar cells to monocyte-depleted mononuclear cells partially reconstituted the response to pokeweed mitogen, whereas the response with higher concentrations of bronchoalveolar cells was similar to background responses. Thus bronchoalveolar cells could modulate pokeweed-nitrogen-induced Ig secretion in different ways, depending on the pressure or absence of monocytes in the mononuclear cell population. The suppressor activities of bronchoalveolar cells were not abrogated by prior irradiation and were only partially reversed by the addition of indomethacin to the cultures. However, prior disruption of bronchoalveolar cells completely abolished their suppressive functions. Suppression of pokeweed-mitogen-induced Ig secretion is probably mediated by intact, radioresistant pulmonary alveolar macrophages.

Defective immunoglobulin secretion in response to pokeweed mitogen in sarcoidosis.

We studied in vitro immunoregulation of immunoglobulin (Ig) secretion in 21 patients with sarcoidosis. While peripheral blood mononuclear cells from normal individuals responded to pokeweed mitogen with a 10-fold or greater increment in Ig-secreting cells, cells from sarcoid patients failed to respond to pokeweed mitogen at any concentration employed (P less than 0.001, Student's t-test, two-tailed). More monocytes were found in sarcoid mononuclear cell preparations (44.8 +/- 2.0% vs 30.4 +/- 1.4% in normal donors, P less than 0.001), but removal of monocytes improved the response to pokeweed mitogen in only four patients. Mononuclear cells from seven of 19 patients suppressed Ig secretion in co-cultures with normal donor cells. Patients exhibiting excessive suppressor cell function were older, with longer standing and less clinically active disease than non-suppressing patients. Monocyte removal reversed the suppression in only four of the suppressor patients, but excessive suppressor monocyte function was later demonstrated in two sarcoid patients whose cells initially did not suppress Ig secretion when cultured with normal cells. While the immunological defects in sarcoidosis may be complex, heterogenous, and dynamic, these data suggest that suppressor monocytes, when present in sarcoidosis, may have developed secondarily.