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Production of type 2 cytokines by CD8+ lung cells is associated with greater decline in pulmonary function in patients with systemic sclerosis.
Arthritis Rheum. 1999 Jun; 42(6):1168-78.AR

Abstract

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.

Authors+Show Affiliations

University of Maryland School of Medicine, and Veterans Affairs Maryland Health Care System, Baltimore 21201, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10366109

Citation

Atamas, S P., et al. "Production of Type 2 Cytokines By CD8+ Lung Cells Is Associated With Greater Decline in Pulmonary Function in Patients With Systemic Sclerosis." Arthritis and Rheumatism, vol. 42, no. 6, 1999, pp. 1168-78.
Atamas SP, Yurovsky VV, Wise R, et al. Production of type 2 cytokines by CD8+ lung cells is associated with greater decline in pulmonary function in patients with systemic sclerosis. Arthritis Rheum. 1999;42(6):1168-78.
Atamas, S. P., Yurovsky, V. V., Wise, R., Wigley, F. M., Goter Robinson, C. J., Henry, P., Alms, W. J., & White, B. (1999). Production of type 2 cytokines by CD8+ lung cells is associated with greater decline in pulmonary function in patients with systemic sclerosis. Arthritis and Rheumatism, 42(6), 1168-78.
Atamas SP, et al. Production of Type 2 Cytokines By CD8+ Lung Cells Is Associated With Greater Decline in Pulmonary Function in Patients With Systemic Sclerosis. Arthritis Rheum. 1999;42(6):1168-78. PubMed PMID: 10366109.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Production of type 2 cytokines by CD8+ lung cells is associated with greater decline in pulmonary function in patients with systemic sclerosis. AU - Atamas,S P, AU - Yurovsky,V V, AU - Wise,R, AU - Wigley,F M, AU - Goter Robinson,C J, AU - Henry,P, AU - Alms,W J, AU - White,B, PY - 1999/6/12/pubmed PY - 2000/4/25/medline PY - 1999/6/12/entrez SP - 1168 EP - 78 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 42 IS - 6 N2 - 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. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/10366109/Production_of_type_2_cytokines_by_CD8+_lung_cells_is_associated_with_greater_decline_in_pulmonary_function_in_patients_with_systemic_sclerosis_ DB - PRIME DP - Unbound Medicine ER -