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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, Cell Communication, Cell Line, Cell Proliferation, Coculture Techniques, Cytokines, Fibroblasts, Humans, Lymphocyte Activation, Middle Aged.
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Does interaction between human lung fibroblasts and T-lymphocytes prevent activation of CD4+ cells? Context: T lymphocytes are demonstrated to play an important role in several chronic pulmonary inflammatory diseases. In this study we provide evidence that human lung fibroblasts are capable of mutually interacting with T-lymphocytes leading to functionally significant responses by T-cells and fibroblasts. Human lung fibroblast were co-cultured with PMA-ionomycin activated T-CD4 lymphocytes for 36 hours. Surface as well as intracellular proteins expression, relevant to fibroblasts and lymphocytes activation, were evaluated by means of flow cytometry and RT-PCR. Proliferative responses of T lymphocytes to concanavalin A were evaluated by the MTT assay. In lung fibroblasts, activated lymphocytes promote an increase of expression of cyclooxygenase-2 and ICAM-1, expressed as mean fluorescence intensity (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 of transcription and protein expression of CD69, LFA-1 and CD28 in activated lymphocytes 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 +/- 1.4 and was significantly reduced by fibroblasts to 6.4 +/- 1.1. Intracellular cytokines, TNF-alpha and IL-10, were evaluated in T lymphocytes. Co-incubation with 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 of T lymphocytes, measured as MTT absorbance, from 0.24 +/- 0.02 nm to 0.16 +/- 0.02 nm. Interestingly, while the activation of fibroblasts is mediated by a soluble factor, a cognate interaction ICAM-1 mediated was demonstrated to be responsible for the modulation of LFA-1, CD28 and CD69.
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Findings from this study suggest that fibroblasts play a role in the local regulation of the immune response, being able to modulate effector functions of cells recruited into sites of inflammation. Final Decision: yes