EXTENSIVE APOPTOSIS OF LUNG T-LYMPHOCYTES MAINTAINED IN-VITRO

The phenotypic and functional properties of T cells recovered from the lung indicate that many of these cells have been recently activated. Because such recently activated cells are often more susceptible to de ath through apoptotic mechanisms, the viability of lung T, cells recov ered from bronchoalveolar lavage and those isolated from peripheral bl ood was compared. The progressive loss of viable cells following in vi tro culture was considerably greater for lavage T cells than blood T c ells, and was observed for cells from both patients with sarcoidosis a nd control subjects. Following 4 days of culture, 76 +/- 14% of blood cells, but only 31 +/- 13% of lavage cells from sarcoid patients were viable. The evaluation of morphologic features and flow cytometric pro files, as well as the demonstration of typical oligonucleosomal fragme ntation of DNA extracted from these cells indicated that lavage T cell s were dying by apoptotic mechanisms. CD4+ T cells appeared to be part icularly sensitive to apoptosis. Most lavage T cells from controls and sarcoid patients expressed Fas (CD95) antigen. Although some lavage T cells were sensitive to Fas-induced apoptosis, the viability of lavag e T cells was not improved by incubation in the presence of a monoclon al antibody that inhibits Fas-induced apoptosis. Culture in the presen ce of interleukin 2 did prevent, at least in part, the progressive dea th of lavage T cells, suggesting that the viability of T cells in the lung may depend on the presence of locally delivered trophic signals. These studies emphasize that T cells on the alveolar surface are in a different state of activation and differentiation compared with that o f circulating T cells, and offer a possible explanation for the impair ed functional capacities observed for lavage T cells in some in vitro studies.