Prognosis of nonspecific interstitial pneumonia correlates with perivascular CD4+ T lymphocyte infiltration of the lung

Abstract

BackgroundNonspecific interstitial pneumonia (NSIP) is characterized by interstitial infiltration of T lymphocytes, and subpopulations of these cells may be associated with the progression of fibrosis. However, few studies evaluate the correlation of prognosis with this characteristic. Therefore, we performed morphological and quantitative analyses of T lymphocytes in patients with NSIP and evaluated the relationship between T lymphocytes and prognosis.MethodsImmunohistochemistry was used to detect the presence of CD4+ and CD8+ T lymphocytes in 55 biopsies of patients with NSIP to determine the numbers of these T cell subpopulations in lymphoid follicles as well as in perivascular, interstitial, and peribronchial anatomical compartments. The relationship between CD4+ and CD8+ T lymphocyte populations and prognosis was analyzed.ResultsThe mean age of 55 patients was 48.9 ± 10.5 years, and 36 (65 %) of patients were women. All patients were followed for a mean duration of 46 ± 25 months. Thirteen (23.6 %) patients died during follow-up. Perivascular CD4+ lymphocyte infiltration (HR, 0.939; 95 % CI, 0.883–0.999; p = 0.048) was an independent risk factor for survival. Perivascular infiltrates of CD4+ T lymphocytes correlated with survival time (r = 0.270, p = 0.046). Patients with improved forced vital capacity survived longer and had higher numbers of CD4+ T lymphocytes that infiltrated perivascular tissue. The densities of CD4+ and CD8+ T lymphocytes infiltrating other tissues were not significantly associated with survival time.ConclusionsPerivascular infiltration of CD4+ T lymphocytes in patients with NSIP correlated with prognosis. The underlying mechanisms are unknown and require further studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-015-0122-z) contains supplementary material, which is available to authorized users.

The Extent of Inflammatory Cell Infiltrate and Fibrosis in Lungs of Telomere- and Surfactant-Related Familial Pulmonary Fibrosis

“…We demonstrated that an inflammatory component was absent in the non-fibrotic areas, suggesting that inflammation does not precede fibrogenesis and may even be reactive to fibrogenesis. Furthermore, in contrast to cNSIP lungs (42,43), we found no association between lymphocytes and survival in FPF lungs, further supporting that the degree of lymphocyte aberrations in FPF lungs may not contribute significantly to disease pathogenesis (26,44). In contrast, it has been reported that elevated numbers of lymphocytes are associated with less progressive fibrosis in patients with sIPF (45,46) and cause resistance to bleomycin in mouse models of pulmonary fibrosis (47).…”

Telomere shortening and fibrotic remodeling in progressive fibrosing interstitial lung disease

“…We demonstrated that an inflammatory component was absent from the non-fibrotic areas, suggesting that inflammation does not precede fibrogenesis and may even be reactive to fibrogenesis. Furthermore, in contrast to cNSIP lungs (85,86), we found no association between lymphocytes and survival in FPF lungs, further supporting the view that the degree of lymphocyte aberrations in FPF lungs may not contribute significantly to disease pathogenesis (64,87). In fact, it has been reported that elevated numbers of lymphocytes are associated with less progressive fibrosis in patients with sIPF (88,89) and cause resistance to bleomycin in mouse models of pulmonary fibrosis (90).…”

“…Telomeres are short TTAGGG DNA tandem repeats at the ends of chromosomes, acting as a buffer in cell-cycle-dependent shortening of DNA, thereby preventing loss of genomic information (83)(84)(85). During healthy aging, leukocyte telomere length declines by approximately 20-30 base pairs per year (86), while in blood leukocytes of patients with pulmonary fibrosis and a TERT mutation telomeres shorten progressively compared to controls and other ILDs (87).…”