Clonal analysis of lung and blood T cells in patients with sarcoidosis.
BACKGROUND
Sarcoidosis is a disease characterised by clinical "anergy" to delayed type hypersensitivity antigens and the formation of non-caseating granulomas, which frequently manifests in the lungs as a T lymphocyte/mononuclear cell alveolitis. Although there is an increased proportion of T cells in bronchoalveolar lavage (BAL) samples from these patients, and these T cells often show evidence of activation and spontaneous secretion of cytokines such as interleukin 2 (IL-2) and interferon gamma (IFN gamma)--a pattern similar to delayed type hypersensitivity reactions--it is unclear whether both cytokines are produced by the majority of T cells derived from the lungs of patients with sarcoidosis or whether unique subpopulations of T cells produce each cytokine. In this study the properties of T cells cloned from BAL fluid samples of patients with sarcoidosis have been analysed.


METHODS
T cells were cloned by limiting dilution using IL-2, phytohaemagglutinin, and irradiated feeder cells. Cloning efficiencies were compared and phytohaemagglutinin induced clonal production of IL-2, IFN gamma, and IL-4 was determined by bioassay (IL-2 and IFN gamma) or ELISA (IL-4).


RESULTS
T cells derived from the BAL fluid of patients with sarcoidosis cloned less efficiently than those from blood of the same individuals. Lung derived clones (CD4+ or CD8+) produced IFN gamma more frequently and to a higher titre than blood derived clones, whereas IL-2 production by CD4+ clones derived from BAL fluid was less than that from blood derived clones. Interestingly, IL-4 production by clones from both sites was similar. Analysis of the co-production of IL-2, IFN gamma, and IL-4 by these BAL fluid clones did not demonstrate a predominant "Th1"-like population which has been suggested to underlie delayed type hypersensitivity reactions.


CONCLUSIONS
The reduced cloning efficiency of T cells from the lung compared with the blood in sarcoidosis is consistent with, although probably more pronounced than, previous observations in normal lungs and shows that T cell hyporesponsiveness is not overcome in the lungs of patients with sarcoidosis. Furthermore, major differences exist between the cytokine producing potential of T cells derived from the lung and the blood in sarcoidosis, and these parallel the differences in the properties of blood and lung T cells seen in healthy individuals.
Department of Medicine, University of Western Australia, Queen Elizabeth II Medical Centre, Nedlands.
M J
MJ
Garlepp
A H
AH
Rose
J E
JE
Dench
B W
BW
Robinson
D000328:Adult; D000368:Aged; D001681:Biological Assay; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008168:Lung / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012507:Sarcoidosis / Q000097:blood / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma