Pulmonary sarcoidosis is a disorder in which local granuloma formation is perpetuated by activated lung T lymphocytes. The present study suggests that lung T lymphocytes may also play a critical role in modulating local production of antibodies in this disorder. In untreated patients with pulmonary sarcoidosis, the numbers of IgG- and IgM-secreting cells per 103 lung lymphocytes are markedly increased compared with those in normal individuals (P < 0.001 and P < 0.01, respectively); the numbers of IgA-secreting cells in lavage fluid of these patients are not increased (P > 0.2). In contrast to lungs, the numbers of IgG-, IgM-, and IgA-secreting cells in blood of patients with this disorder are similar to those in normal individuals (P > 0.2, each comparison). In patients with pulmonary sarcoidosis, there is a direct correlation between the percentage of bronchoalveolar cells that are T lymphocytes and the percentage of bronchoalveolar cells that secrete IgG (r = 0.79; P < 0.001); in normal individuals there is no such relationship (P > 0.2). When purified sarcoid lung T cells from patients with high proportions of T lymphocytes in their lavage fluid were co-cultured with blood mononuclear cells from normal individuals (without added antigens or mitogens), the B lymphocytes in these normal mononuclear cell suspensions were induced to differentiate into immunoglobulin-secreting cells (P < 0.01). In contrast, blood T lymphocytes from these same patients and lung T lymphocytes from sarcoidosis patients with low proportions of T lymphocytes in their lavage fluid did not stimulate normal B cells to produce immunoglobulin (P > 0.2, all comparisons). These findings suggest that in pulmonary sarcoidosis (a) the lung is an important site of immunoglobulin production; (b) activated lung T lymphocytes play an important role in modulating this local production of antibody, and thus are likely to modulate the polyclonal hyperglobulinemia observed in these individuals.
Gary W. Hunninghake, Ronald G. Crystal