Production of type 2 cytokines by CD8+ lung cells is associated with greater decline in pulmonary function in patients with systemic sclerosis
✍ Scribed by Sergei P. Atamas; Vladimir V. Yurovsky; Robert Wise; Fredrick M. Wigley; Carol J. Goter Robinson; Patricia Henry; William J. Alms; Barbara White
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 206 KB
- Volume
- 42
- Category
- Article
- ISSN
- 0004-3591
No coin nor oath required. For personal study only.
✦ Synopsis
Objective:
This study addresses the hypothesis that a profibrotic pattern of cytokines is produced in the lungs of patients with systemic sclerosis (ssc) and causes fibrosis.
Methods:
Using a reverse transcriptase-polymerase chain reaction technique, interleukin-4 (il-4), il-5, and interferon-gamma (ifngamma) messenger rna (mrna) were measured in unseparated cd8+ and cd4+ bronchoalveolar lavage (bal) cells from ssc patients and healthy controls. to confirm the results, cd8+ t cells were cloned from bal fluids, and the pattern of cytokine mrna made by these cells was determined. serial pulmonary function tests were done.
Results:
Bal cells from healthy controls made ifngamma mrna, with no or little il-4 or il-5 mrna. in contrast, bal cells from the majority of ssc patients made il-4 and/or il-5 mrna, with or without approximately equal amounts of ifngamma mrna. this pattern of cytokines was made by cd8+ t cells, which were increased in the lungs of these ssc patients. patients whose bal cells made this type 2 pattern of cytokine mrna had a significant decline in forced vital capacity over time after the bal, whereas patients whose bal cells made ifngamma mrna alone did not. both wild-type and an alternative splice variant of il-4 mrna were increased in bal cells from ssc patients. both forms of il-4 stimulated alpha2(i) collagen mrna in human dermal and lung fibroblasts.
Conclusion:
The type 2 pattern of cytokine mrna produced by bal cells from ssc patients differs from unopposed ifngamma production found in healthy bal cells. this production of type 2 cytokine mrna by cd8+ t cells is associated with a significant decline in lung function over time, which suggests a pathologic role for these t cells in interstitial fibrosis in ssc.