Helper T-lymphocytes in pulmonary sarcoidosis. Functional analysis of a lung T-cell subpopulation in patients with active disease

Pulmonary sarcoidosis is a disease characterized by increased numbers of T-lymphocytes in the alveolar structures, which through the production of lymphokines modulate granuloma formation and polyclonally activate B cells to secrete immunoglobulins. The T-lymphocyte alveolitis is associated with a different expansion of various T-cell subpopulations identified by different monoclonal antibodies. Patients with active disease have increased numbers of helper T cells in the lungs, recognized by the OKT4 monoclonal antibody and decreased numbers of supressor OKT8-positive lung T cells, whereas patients with inactive disease have increased numbers of OKT8-positive T cells and decreased numbers of OKT4-positive T cells in the lungs. Using the IgG fraction of a monoclonal antibody called 5/9, which reacts in normal subjects with approximately 30% of the OKT4-positive T-lymphocytes, it has been shown that the 5/9-positive T cells appear preferentially expanded in pulmonary sarcoidosis at sites of disease activity. To evaluate the functions of the T-cell subpopulation identified by the 5/9 monoclonal antibody in pulmonary sarcoidosis, we studied the unfractionated T-lymphocytes and the 5/9-positive and the 5/9-negative T-cell fractions in bronchoalveolar lavage of 12 patients with active lung disease. On T-cell suspensions, the spontaneous release of monocyte chemotactic factor and the polyclonal activation of autologous peripheral blood lymphocytes were determined. The concentrations of monocyte chemotactic factor were similar in the supernatants of unfractionated lung T-lymphocytes and in the 5/9-positive lung T-cell fraction (p > 0.05) but lower in the supernatants of the 5/9-negative lung T-cell subpopulation when compared with supernatants of unfractionated lung T cells or of 5/9-positive lung T cells (p <0.001, all comparisons). In addition, the helper activity for autologous B-cell differentiation shown by the unfractionated lung T-lymphocytes appeared to be restricted to the 5/9-positive lung T-cell subpopulation, because unfractionated lung T cells and 5/9-positive lung T cells induced the secretion of comparable amounts of immunoglobulins, whereas no help to B cells was provided by the 5/9-negative lung T cells. Thus, active pulmonary sarcoidosis is characterized by the expansion of a helper T-cell subpopulation in the alveolar structures, the 5/9-positive lung T cells, which is responsible for 2 major T-cell functions relevant to the pathogenesis of this disorder.