ANTIGEN-INDUCED PROLIFERATIVE RESPONSE OF LAVAGE AND BLOOD LYMPHOCYTE-T - COMPARISON OF CELLS FROM NORMAL SUBJECTS AND PATIENTS WITH SARCOIDOSIS

To evaluate the mechanisms responsible for energy in sarcoid patients, we studied the ability of highly purified lavage and blood T lymphocytes from control subjects and patients with sarcoidosis to proliferate in response to recall antigens, and compared the results of antigen-induced lymphocyte proliferation with the clinical characteristics of the patients. Both blood and lavage T lymphocytes from all control subjects proliferated in response to purified protein derivative (PPD) and candida antigens, and no significant difference was observed comparing the proliferation of lymphocytes from the two sources. The antigen-induced proliferation of blood and lavage T lymphocytes from sarcoid patients was reduced compared with that of the corresponding cell poulations from normal subjects (p < 0.01 for PPD, Candida, and tetanus), and the proliferative response of sarcoid lavage lymphocytes was significantly lower than that of blood T lymphocytes from these patients. No evidence for inhibition of T lymphocyte proliferation by accessory cells (blood monocytes) or CD8+ T lymphocytes was observed, and the refractory state could not be overcome by adding exogenous recombinant human IL-2 or IL-4. An inverse correlation was observed between the PPD-induced proliferation of sarcoid lavage T lymphocytes and criteria associated with "active" disease, including lymphocytes/ml lavage fluid (p < 0.003), Ga-67 uptake (p < 0.005), and serum angiotensin converting enzyme activity (p < 0.005). Lavage lymphocytes from patients studied early in the course of the disease proliferated better than those from patients with more long-standing disease. We conclude that the inhibition of responsiveness of memory T lymphocytes to recall antigens, although not necessarily an early event, is an integral part of the immune response in active sarcoidosis and likely contributes to the anergy observed in these patients.