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 death through apoptotic mechanisms, the viability of lung T cells recovered from bronchoalveolar lavage and those isolated from peripheral blood was compared. The progressive loss of viable cells following in vitro culture was considerably greater for lavage T cells than blood T cells, and was observed for cells from both patients with sarcoidosis and 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 profiles, as well as the demonstration of typical oligonucleosomal fragmentation of DNA extracted from these cells indicated that lavage T cells were dying by apoptotic mechanisms. CD4+ T cells appeared to be particularly 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 lavage T cells was not improved by incubation in the presence of a monoclonal antibody that inhibits Fas-induced apoptosis. Culture in the presence of interleukin 2 did prevent, at least in part, the progressive death 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 of circulating T cells, and offer a possible explanation for the impaired functional capacities observed for lavage T cells in some in vitro studies.
Herry
I
I
INSERM U.82, Faculté de Médecine Xavier Bichat, Paris, France.
Bonay
M
M
Bouchonnet
F
F
Schuller
M P
MP
Lecossier
D
D
Tazi
A
A
Lynch
D H
DH
Hance
A J
AJ
D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured / Q000166:cytology / Q000276:immunology; D053938:DNA Fragmentation / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000494:pharmacology; D008168:Lung / Q000166:cytology* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012507:Sarcoidosis / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology*; D019014:fas Receptor / Q000502:physiology
D007376:Interleukin-2; D019014:fas Receptor