T-lymphocytes recovered by bronchoalveolar lavage from normal subjects and patients with sarcoidosis are refractory to proliferative signals.
Granuloma formation in the lung of patients with sarcoidosis is preceded by the accumulation of large numbers of activated T-lymphocytes, which results, at least in part, from the proliferation of T-lymphocytes within the lung. To determine whether the increased proliferation of lung T-lymphocytes in sarcoidosis results from a failure of mechanisms responsible for limiting their proliferation, we have compared the ability of purified T-lymphocytes present in bronchoalveolar lavage fluid and peripheral blood from normal subjects and patients with sarcoidosis to respond to proliferative signals. The mitogen-induced proliferative response of lavage T-lymphocytes from normal subjects and patients with sarcoidosis was similar, but the response of lavage T-lymphocytes was much less than that observed using normal or sarcoid blood T-lymphocytes. The reduced proliferative response of sarcoid lavage T-lymphocytes could not be overcome by addition of accessory cells or exogenous interleukin-2, and it did not result from the presence of suppressor cells. Furthermore, sarcoid lavage lymphocytes are capable of being activated by "mitogenic" signals, as indicated by the ability of phytohemagglutinin to induce expression of the 4F2 surface antigen and stimulate interleukin-2 production. However, the expression of interleukin-2 receptors was reduced on stimulated sarcoid lavage T-lymphocytes compared with that observed on normal blood T-lymphocytes, which may account in part for their reduced proliferative capacity. Because mechanisms that render lavage T-lymphocytes from normal subjects refractory to proliferative signals appear to operate in sarcoidosis as well, these findings suggest that a defect in the inhibition of T-lymphocyte proliferation is unlikely to be an important cause of lymphocyte accumulation in this disorder.
Lecossier
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D
INSERM U.82, Faculté Xavier Bichat, Paris, France.
Valeyre
D
D
Loiseau
A
A
Battesti
J P
JP
Soler
P
P
Hance
A J
AJ
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D002455:Cell Division; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000502:physiology; D008171:Lung Diseases / Q000097:blood / Q000473:pathology*; D008285:Major Histocompatibility Complex; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D011946:Receptors, Antigen; D012507:Sarcoidosis / Q000097:blood / Q000473:pathology*; D013601:T-Lymphocytes / Q000473:pathology*
D007376:Interleukin-2; D010835:Phytohemagglutinins; D011946:Receptors, Antigen; D003208:Concanavalin A