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T cell independence of bleomycin-induced pulmonary fibrosis
M Helene1, V Lake-Bullock, J Zhu
1Department of Microbiology & Immunology, University of Kentucky, College of Medicine, Lexington 40536, USA.
Abstract:
The role of T cells and cytokines in bleomycin (BLM)-induced fibrosis was evaluated in susceptible and resistant strains of normal and SCID mice. Histology and hydroxyproline analysis showed that BLM induced pulmonary fibrosis in C57BL/6 and (C57BL/6 x BALB/c)F1 mice, whereas BALB/c mice were resistant to the disease. To test whether lymphocytes were required for the induction of BLM-induced pulmonary fibrosis, SCID mice were injected intratracheally with BLM and evaluated for the development of pulmonary inflammation and fibrosis. Similar morphological changes and increases in hydroxyproline were observed in both C57BL/6 SCID and (C57BL/6 x CB.17)F1 SCID animals compared to those seen in wild-type C57BL/6 and (C57BL/6 x BALB/c)F1 mice. In contrast, CB.17 SCID mice, which are genetically similar to BALB/c mice, were resistant to disease induction. Analysis of the cellular infiltrate in BLM-treated C57Bl/6 SCID mice confirmed a lack of T cells in the lungs of SCID mice and demonstrated a pronounced accumulation of eosinophils in areas of developing pulmonary fibrosis. NK cells were significantly elevated in untreated SCID mice and did not increase further after BLM treatment. Analysis of selected cytokines 1 day after initiation of BLM-induced pulmonary fibrosis indicated that the levels of TNF-alpha and IFN-gamma appeared to segregate with fibrosis in both the SCID and wild-type mice. The data demonstrate that T cells are not required for the induction of fibrosis by BLM and suggest that responses by non-lymphoid cells may be sufficient for the induction of fibrosis.
Insights
T cells are not required for bleomycin-induced lung fibrosis. Non-lymphoid cells, like eosinophils, may be sufficient for fibrosis development, even in T-cell deficient mice.
Area of Science:
- Immunology
- Pulmonary Medicine
- Fibrosis Research
Background:
- Bleomycin (BLM) is a chemotherapeutic agent known to induce pulmonary fibrosis.
- The precise immunological mechanisms underlying BLM-induced fibrosis, particularly the role of T cells and cytokines, remain incompletely understood.
Purpose of the Study:
- To investigate the necessity of T cells and the involvement of cytokines in the pathogenesis of bleomycin-induced pulmonary fibrosis.
- To compare the fibrotic response in susceptible and resistant mouse strains, including severe combined immunodeficient (SCID) models.
Main Methods:
- Pulmonary fibrosis was induced using bleomycin in various mouse strains (C57BL/6, BALB/c) and their SCID counterparts.
- Histological analysis and hydroxyproline content measurements were used to quantify fibrosis.
- Cellular infiltrates and cytokine levels (TNF-alpha, IFN-gamma) were analyzed in lung tissues.
Main Results:
- Bleomycin induced pulmonary fibrosis in susceptible mouse strains (C57BL/6) but not in resistant strains (BALB/c).
- SCID mice, lacking T cells, developed pulmonary fibrosis comparable to wild-type mice, indicating T cells are not essential for fibrosis induction.
- A significant accumulation of eosinophils was observed in the lungs of BLM-treated SCID mice, suggesting their potential role in fibrosis.
- Cytokine levels of TNF-alpha and IFN-gamma correlated with fibrosis development in both SCID and wild-type mice.
Conclusions:
- T cells are not required for the induction of bleomycin-induced pulmonary fibrosis.
- Non-lymphoid cellular responses, potentially involving eosinophils, may be sufficient to drive fibrosis.
- Cytokines like TNF-alpha and IFN-gamma play a role in the fibrotic process, irrespective of T cell presence.