[Studies on the responsiveness of alveolar T cells to proliferative stimuli and on surface antigens].
Lymphocyte alveolitis which can be detected by bronchoalveolar lavage is a characteristic feature of pulmonary sarcoidosis and has been thought to be a latent or preceding pathogenetic process of granuloma formation in the lung. To explore the mechanism of this lymphocyte accumulation, the capacity of alveolar T cells obtained from patients with pulmonary sarcoidosis to release interleukin-2 (IL-2) was assessed and compared with that of autologous peripheral blood T cells. Contrary to previous reports, spontaneous production of IL-2 by unstimulated alveolar T cells was not observed. When stimulated with phytohemagglutinin (PHA), alveolar T cells released considerable amounts of IL-2, however, still less than blood T cells. We next measured intracytoplasmic free calcium ion concentrations ([Ca2+]i) which are intimately related to cell activation triggered by proliferative stimuli. Alveolar T cells in patients with pulmonary sarcoidosis showed lowered responses of [Ca2+]i than blood T cells when stimulated with PHA, thus, demonstrating PHA-hyporesponsiveness at the second messenger level. Meanwhile, [Ca2+]i response of alveolar T cells stimulated with anti-CD3 antibody was higher than that of blood T cells. To investigate mechanisms underlying this unique responsiveness of alveolar T cells, we first examined cell surface expression of alpha beta T cell receptor (TCR). Flow cytometric analysis showed reduced expression of TCR by alveolar T cells compared with blood T cells, a phenomenon commonly called modulation. Since modulation of TCR/CD3 molecular complex is reportedly associated with T cell hyporesponsiveness to lectins, modulation appeared to account, in part, for the reduced IL-2 release by PHA-stimulated alveolar T cells. On the other hand, the present study revealed that memory T cells were dominant among alveolar T cells. This fact also seemed to be responsible for contrasting responses of [Ca2+]i to PHA and anti-CD3 antibody mentioned above, since mitogenic response of memory T cells coincide well with [Ca2+]i response of alveolar T cells. Interestingly and importantly enough, both modulation and memory T cell-dominancy in alveolar T cells were also observed in normal subjects. Accordingly, these findings suggest that responsiveness of alveolar T cells to mitogenic stimuli observed for patients with sarcoidosis is a feature shared by alveolar T cells in health and disease. Thus, present study revealed characteristics of alveolar T cells in general taking advantage of investigation of IL-2 production by alveolar T cells in sarcoidosis.
First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
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Yamaguchi
D000328:Adult; D000954:Antigens, Surface / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002118:Calcium; D002455:Cell Division; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008171:Lung Diseases / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology*; D012507:Sarcoidosis / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D000954:Antigens, Surface; D007376:Interleukin-2; D010835:Phytohemagglutinins; D002118:Calcium