Interaction between human lung fibroblasts and T-lymphocytes prevents activation of CD4+ cells

T lymphocytes are demonstrated to play an important role in severalchronic pulmonary inflammatory diseases. In this study we provide evidence thathuman lung fibroblasts are capable of mutually interacting with T-lymphocytesleading to functionally significant responses by T-cells and fibroblasts.METHODS: Human lung fibroblast were co-cultured with PMA-ionomycin activatedT-CD4 lymphocytes for 36 hours. Surface as well as intracellular proteinsexpression, relevant to fibroblasts and lymphocytes activation, were evaluated bymeans of flow cytometry and RT-PCR. Proliferative responses of T lymphocytes toconcanavalin A were evaluated by the MTT assay.RESULTS: In lung fibroblasts, activated lymphocytes promote an increase ofexpression of cyclooxygenase-2 and ICAM-1, expressed as mean fluorescenceintensity (MFI), from 5.4 +/- 0.9 and 0.7 +/- 0.15 to 9.1 +/- 1.5 and 38.6 +/-7.8, respectively. Fibroblasts, in turn, induce a significant reduction oftranscription and protein expression of CD69, LFA-1 and CD28 in activatedlymphocytes and CD3 in resting lymphocytes. In activated T lymphocytes, LFA-1,CD28 and CD69 expression was 16.6 +/- 0.7, 18.9 +/- 1.9 and 6.6 +/- 1.3,respectively, and was significantly reduced by fibroblasts to 9.4 +/- 0.7, 9.4+/- 1.4 and 3.5 +/- 1.0. CD3 expression in resting lymphocytes was 11.9 +/- 1.4and was significantly reduced by fibroblasts to 6.4 +/- 1.1. Intracellularcytokines, TNF-alpha and IL-10, were evaluated in T lymphocytes. Co-incubationwith fibroblasts reduced the number of TNF-alpha positive lymphocytes from 54.4% +/- 6.12 to 30.8 +/- 2.8, while IL-10 positive cells were unaffected. Finally,co-culture with fibroblasts significantly reduced Con A proliferative response ofT lymphocytes, measured as MTT absorbance, from 0.24 +/- 0.02 nm to 0.16 +/- 0.02nm. Interestingly, while the activation of fibroblasts is mediated by a solublefactor, a cognate interaction ICAM-1 mediated was demonstrated to be responsible for the modulation of LFA-1, CD28 and CD69.CONCLUSION: Findings from this study suggest that fibroblasts play a role in the local regulation of the immune response, being able to modulate effectorfunctions of cells recruited into sites of inflammation