亚急性和慢性过敏性肺炎中T细胞亚群的功能多样性

Functional diversity of T-cell subpopulations in subacute and chronic hypersensitivity pneumonitis.

作者信息

Barrera Lourdes, Mendoza Felipe, Zuñiga Joaquín, Estrada Andrea, Zamora Ana C, Melendro Emma I, Ramírez Remedios, Pardo Annie, Selman Moisés

机构信息

Instituto Nacional de Enfermedades Respiratorias, Tlalpan 4502, CP 14080, Mexico DF, Mexico.

出版信息

Am J Respir Crit Care Med. 2008 Jan 1;177(1):44-55. doi: 10.1164/rccm.200701-093OC. Epub 2007 Oct 18.

DOI:10.1164/rccm.200701-093OC

PMID:17947613

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.

摘要

理论依据

过敏性肺炎（HP）呈现出多样的结局。急性/亚急性HP患者通常会好转，而患有慢性疾病的患者往往会进展为肺纤维化。然而，这种差异背后的机制尚不清楚。

目的

研究亚急性HP和慢性HP患者的T细胞谱。

方法

通过支气管肺泡灌洗从25例亚急性HP患者、30例慢性HP患者和8名对照受试者中获取T细胞。通过流式细胞术、细胞计数珠阵列和免疫组织化学评估T细胞表型和功能谱。

测量指标和主要结果

慢性HP患者的CD4⁺:CD8⁺比值更高（中位数为3.05；范围为0.3 - 15；亚急性HP：中位数为1.3；范围为0.1 - 10；对照：中位数为1.3；范围为0.7 - 2.0；P < 0.01），且γδT细胞减少（中位数为2.0；范围为0.5 - 3.4；亚急性HP：中位数为10；范围为4.8 - 17；对照：中位数为15；范围为5 - 19；P < 0.01）。与亚急性HP患者相比，慢性HP患者终末分化记忆CD4⁺和CD8⁺T细胞亚群增加（P < 0.05）。然而，慢性HP患者的记忆细胞产生的IFN - γ较低，且CD8⁺T淋巴细胞的细胞毒性活性降低。慢性HP表现出类似Th2的表型，CXCR4表达增加（中位数为6%；范围为1.7 - 36，与对照受试者相比：中位数为0.7%；范围为0.2 - 1.4；亚急性HP：中位数为2.2%；范围为0.1 - 5.3；P < 0.01），而CXCR3表达降低（中位数为4.3%；范围为1.4 - 25%，与亚急性HP相比：中位数为37%；范围为4.9 - 78%；P < 0.01）。同样，与亚急性HP相比，慢性HP抗原特异性刺激细胞的上清液中IL - 4水平更高（80 ± 63 pg/ml对25 ± 7 pg/ml；P < 0.01），IFN - γ水平更低（3818 ± 1671 pg/ml对100 ± 61 pg/ml；P < 0.01）。