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Functional diversity of T-cell subpopulations in subacute and chronic hypersensitivity pneumonitis.
Am J Respir Crit Care Med. 2008 Jan 01; 177(1):44-55.AJ

Abstract

RATIONALE

Hypersensitivity pneumonitis (HP) exhibits a diverse outcome. Patients with acute/subacute HP usually improve, whereas patients with chronic disease often progress to fibrosis. However, the mechanisms underlying this difference are unknown.

OBJECTIVES

To examine the T-cell profile from patients with subacute HP and chronic HP.

METHODS

T cells were obtained by bronchoalveolar lavage from 25 patients with subacute HP, 30 patients with chronic HP, and 8 control subjects. T-cell phenotype and functional profile were evaluated by flow cytometry, cytometric bead array, and immunohistochemistry.

MEASUREMENTS AND MAIN RESULTS

Patients with chronic HP showed higher CD4+:CD8+ ratio (median, 3.05; range, 0.3-15; subacute HP: median, 1.3; range, 0.1-10; control: median, 1.3; range, 0.7-2.0; P < 0.01), and a decrease of gammadeltaT cells (median, 2.0; range, 0.5-3.4; subacute HP: median, 10; range, 4.8-17; control: median, 15; range, 5-19; P < 0.01). Patients with chronic HP exhibited an increase in the terminally differentiated memory CD4+ and CD8+ T-cell subsets compared with patients with subacute HP (P < 0.05). However, memory cells from chronic HP showed lower IFN-gamma production and decreased cytotoxic activity by CD8+ T lymphocytes. Chronic HP displayed a Th2-like phenotype with increased CXCR4 expression (median, 6%; range, 1.7-36, vs. control subjects: median, 0.7%; range, 0.2-1.4; and subacute HP: median, 2.2%; range, 0.1-5.3; P < 0.01), and decreased CXCR3 expression (median, 4.3%; range, 1.4-25%, vs. subacute HP: median, 37%; range, 4.9-78%; P < 0.01). Likewise, supernatants from antigen-specific-stimulated cells from chronic HP produced higher levels of IL-4 (80 +/- 63 pg/ml vs. 25 +/- 7 pg/ml; P < 0.01), and lower levels of IFN-gamma (3,818 +/- 1671 pg/ml vs. 100 +/- 61 pg/ml; P < 0.01) compared with subacute HP.

CONCLUSIONS

Our findings indicate that patients with chronic HP lose effector T-cell function and exhibit skewing toward Th2 activity, which may be implicated in the fibrotic response that characterizes this clinical form.

Authors+Show Affiliations

Instituto Nacional de Enfermedades Respiratorias, Tlalpan 4502, CP 14080, Mexico DF, Mexico.No affiliation info availableNo 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

Language

eng

PubMed ID

17947613

Citation

Barrera, Lourdes, et al. "Functional Diversity of T-cell Subpopulations in Subacute and Chronic Hypersensitivity Pneumonitis." American Journal of Respiratory and Critical Care Medicine, vol. 177, no. 1, 2008, pp. 44-55.
Barrera L, Mendoza F, Zuñiga J, et al. Functional diversity of T-cell subpopulations in subacute and chronic hypersensitivity pneumonitis. Am J Respir Crit Care Med. 2008;177(1):44-55.
Barrera, L., Mendoza, F., Zuñiga, J., Estrada, A., Zamora, A. C., Melendro, E. I., Ramírez, R., Pardo, A., & Selman, M. (2008). Functional diversity of T-cell subpopulations in subacute and chronic hypersensitivity pneumonitis. American Journal of Respiratory and Critical Care Medicine, 177(1), 44-55.
Barrera L, et al. Functional Diversity of T-cell Subpopulations in Subacute and Chronic Hypersensitivity Pneumonitis. Am J Respir Crit Care Med. 2008 Jan 1;177(1):44-55. PubMed PMID: 17947613.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functional diversity of T-cell subpopulations in subacute and chronic hypersensitivity pneumonitis. AU - Barrera,Lourdes, AU - Mendoza,Felipe, AU - Zuñiga,Joaquín, AU - Estrada,Andrea, AU - Zamora,Ana C, AU - Melendro,Emma I, AU - Ramírez,Remedios, AU - Pardo,Annie, AU - Selman,Moisés, Y1 - 2007/10/18/ PY - 2007/10/20/pubmed PY - 2008/1/8/medline PY - 2007/10/20/entrez SP - 44 EP - 55 JF - American journal of respiratory and critical care medicine JO - Am J Respir Crit Care Med VL - 177 IS - 1 N2 - RATIONALE: Hypersensitivity pneumonitis (HP) exhibits a diverse outcome. Patients with acute/subacute HP usually improve, whereas patients with chronic disease often progress to fibrosis. However, the mechanisms underlying this difference are unknown. OBJECTIVES: To examine the T-cell profile from patients with subacute HP and chronic HP. METHODS: T cells were obtained by bronchoalveolar lavage from 25 patients with subacute HP, 30 patients with chronic HP, and 8 control subjects. T-cell phenotype and functional profile were evaluated by flow cytometry, cytometric bead array, and immunohistochemistry. MEASUREMENTS AND MAIN RESULTS: Patients with chronic HP showed higher CD4+:CD8+ ratio (median, 3.05; range, 0.3-15; subacute HP: median, 1.3; range, 0.1-10; control: median, 1.3; range, 0.7-2.0; P < 0.01), and a decrease of gammadeltaT cells (median, 2.0; range, 0.5-3.4; subacute HP: median, 10; range, 4.8-17; control: median, 15; range, 5-19; P < 0.01). Patients with chronic HP exhibited an increase in the terminally differentiated memory CD4+ and CD8+ T-cell subsets compared with patients with subacute HP (P < 0.05). However, memory cells from chronic HP showed lower IFN-gamma production and decreased cytotoxic activity by CD8+ T lymphocytes. Chronic HP displayed a Th2-like phenotype with increased CXCR4 expression (median, 6%; range, 1.7-36, vs. control subjects: median, 0.7%; range, 0.2-1.4; and subacute HP: median, 2.2%; range, 0.1-5.3; P < 0.01), and decreased CXCR3 expression (median, 4.3%; range, 1.4-25%, vs. subacute HP: median, 37%; range, 4.9-78%; P < 0.01). Likewise, supernatants from antigen-specific-stimulated cells from chronic HP produced higher levels of IL-4 (80 +/- 63 pg/ml vs. 25 +/- 7 pg/ml; P < 0.01), and lower levels of IFN-gamma (3,818 +/- 1671 pg/ml vs. 100 +/- 61 pg/ml; P < 0.01) compared with subacute HP. CONCLUSIONS: Our findings indicate that patients with chronic HP lose effector T-cell function and exhibit skewing toward Th2 activity, which may be implicated in the fibrotic response that characterizes this clinical form. SN - 1535-4970 UR - https://www.unboundmedicine.com/medline/citation/17947613/Functional_diversity_of_T_cell_subpopulations_in_subacute_and_chronic_hypersensitivity_pneumonitis_ L2 - https://www.atsjournals.org/doi/10.1164/rccm.200701-093OC?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -