Human lung fibroblasts increase CD4(+)CD25(+)Foxp3(+) T cells in co-cultured CD4(+) lymphocytes.
Aim of this study was to evaluate functional modifications induced by human lung fibroblasts in co-cultured CD4(+) T lymphocytes. CD4(+) T cells, resting or stimulated with ionomycin/PMA for 6h, were co-cultured with fibroblasts isolated from pulmonary biopsies, in contact or separated by a semi-permeable membrane. The expression of CD25, CTLA-4, TGF-β, IFNγ, IL-2, IL-4, IL-10 and Foxp3 was evaluated by flow cytometric analysis. Fibroblasts induced a significant increment in CD25(+) cells in co-cultured activated CD4(+) T lymphocytes separated by a membrane. Moreover, fibroblasts treatment with a COX2 inhibitor abrogated the increment in CD25(+) cells whereas exogenous PGE2 restored it. The CD25(+) subpopulation was characterized by increased presence of Fox-P3, CTLA-4, IL-10 and TGF-β positive cells while IFN-γ and IL-2 positive cells were diminished. Proliferative response of CD4(+) to the anti CD3/CD28-Abs was abrogated in CD4(+) co-cultured with fibroblasts thus demonstrating a suppressive feature of the expanded CD25(+) subpopulation.
Department of Clinical and MolecularBiomedicine, University of Catania, Catania, Italy. Electronic address: econte@unict.it.
Enrico
E
Conte
Elisa
E
Gili
Mary
M
Fruciano
Evelina
E
Fagone
Carlo
C
Vancheri
D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D060908:CTLA-4 Antigen / Q000378:metabolism; D049109:Cell Proliferation; D018920:Coculture Techniques; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015759:Ionomycin; D008168:Lung / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism
D018106:CD28 Antigens; D017252:CD3 Complex; D060908:CTLA-4 Antigen; D052246:Cyclooxygenase 2 Inhibitors; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4; D015759:Ionomycin; D007371:Interferon-gamma; D015232:Dinoprostone
Human lung fibroblasts; PGE(2); T regulatory cells