The repertoire of T-lymphocytes recovered by bronchoalveolar lavage from healthy nonsmokers (original) (raw)
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A clonal analysis of lung T cells derived by bronchoalveolar lavage of healthy individuals
Immunology, 1992
The characteristics of the T-cell population in the healthy human lung have been investigated by analysing the properties of T-cell clones derived from bronchoalveolar lavage (BAL) samples and comparing them with T cells cloned from the blood of the same individuals. The proportions of CD4+ and CD8+ T cells in the starting populations from BAL and blood were similar although only 14% of BAL T cells were CD45RA+ compared to 70% of blood T cells. The precursor frequency of T-cell clones derived from BAL was less than from blood. The cytokine profiles [after phytohaemagglutinin (PHA) stimulation] of the clones derived from both sources were markedly different and these differences lay in the CD4+ population. BAL-derived CD4+ clones produced interferon-gamma (IFN-gamma) more frequently than did those from blood while blood-derived clones were more likely to produce interleukin-2 (IL-2) than those from BAL. IL-4 was produced by the majority of BAL- or blood-derived clones (93% and 88% re...
Immunocompetent cells from the lower respiratory tract of normal human lungs
Journal of Clinical Investigation, 1975
A B S T R A C T Subpopulations of lymiphocytes in the broncho-alveolar air spaces of normal human lungs were compared with those in peripheral blood. Bone marrowderived (bursal-equivalent) cells (B cells) were identified by complement receptors (EAC rosettes) and by surface immunoglobulin. Thymus-derived lymphocytes (T cells) were identified by their proliferative response to mitogens and the E rosette technique.
Frequency of allergen-specific T lymphocytes in blood and bronchial response to allergen in asthma
Journal of Allergy and Clinical Immunology, 1993
This study was designed to investigate whether the bronchial response to the sensitizing allergen in asthma is correlated with the frequency of allergen-specific T lymphocytes. Twenty-three asthmatic patients sensitized to Dermatophagoides pteryonyssinus who had never received hyposensitizing therapy and 11 healthy control subjects were studied. Allergen-specific T lymphocytes were enumerated in peripheral blood with limiting dilution cultures. Bronchial challenge with methacholine was performed in all subjects; patients with asthma also underwent an allergen bronchial challenge. Correlations between allergen-specific T cell frequencies and nonspecific bronchial hyperresponsiveness to methacholine as independent variables and early and late bronchial responsiveness to allergen challenge as dependent variables were investigated by means of stepwise-multiple regression analysis. We found that the frequency of allergen-specific T lymphocytes was higher than in control subjects in both patients with asthma with (p < 0.001) and those without (p < 0.05) late-phase asthmatic response to allergen. Moreover, the provocative does of allergen necessary to produce an early 15% fall of forced expiratory volume in 1 second could be predicted in part (59%) by an equation that incorporates methacholine sensitivity and allergen-specific T cell frequency. We conclude that allergen-specific T lymphocytes, which have an established influence on immunoglobulin E production, play an additional role in the induction of the bronchospastic response to inhaled allergen.
T cells in the lung of patients with hypersensitivity pneumonitis accumulate in a clonal manner
Journal of Leukocyte Biology, 2003
Removal from antigenic exposure led to the disappearance of T cell clones. Our findings indicate that expansions of T lymphocytes bearing clonal TCRBV region gene segments take place in the lung of patients with HP during exposure. The evidence that identical T cell clones are present in the lung and the blood of the same patient suggests that the immune reaction occurring at lung level gives rise to a systemic reaction. J. Leukoc. Biol. 75: 798 -804; 2004.
Lung and blood T cell repertoire in extrinsic allergic alveolitis
European Respiratory Journal
Patients with extrinsic allergic alveolitis (EAA) have accumulations of T-lymphocytes in their lungs. CD8+ lung T-cells, in particular, have been implicated in the pathogenesis of EAA. The objective of the present study was to analyse the T-cell receptor (TCR) Vα and Vβ gene usage of CD4+ and CD8+ lung and peripheral blood lymphocytes (PBLs) before and after treatment.
Clonal Expansion of Allergen-specific CD4(+) T Cell in the Lung in the Absence of Lymph Nodes
Immune network, 2017
The expansion of allergen-specific CD4(+) T cells is a critical step in inducing airway inflammation during allergic asthma. Such clonal expansion of T cells is initiated through the interaction between allergen-bearing dendritic cells and allergen-specific naïve T cells in the draining lymph nodes. Whether such T cell clonal expansion also occurs in the lung, the primary organ encountering inhaled allergens, remains unclear. Compared with wild-type mice, we found similar frequencies of CD4(+) T cells in the lung of lymph node-deficient Rorgt(gfp/gfp) mice after repeated exposure to inhaled allergens. In addition, we observed an evident population of CD4(+) T cells that underwent clonal expansion in the lung of allergen-challenged mice treated with an S1P antagonist FTY720 in an in vivo proliferation study with CFSE-labeled OT-II T cells. Moreover, the expansion of allergen-specific CD4(+) T cells was significantly enhanced in the lungs of Rorgt(gfp/gfp) mice in comparison to that o...
T lymphocytes in asthma: Bronchial versus peripheral responses
Journal of Allergy and Clinical Immunology, 2000
Recent evidence points to the recruitment of T H 2 cells, phenotype T lymphocytes, their activation, and the generation of T H 2 cytokines, particularly IL-4 and IL-5, in both peripheral blood and bronchial mucosa of asthmatic patients, leading to local tissue eosinophilia and IgE-dependent mast-cell activation. Activation of T H 2 T lymphocytes appears to be specific for asthma (as opposed to airway obstructive disease) and was shown to correlate with asthma severity as evidenced by the inverse correlation between CD25 + /CD4 + cells and peak expiratory flow rates. These findings support the fundamental importance of T-lymphocyte responses in bronchial asthma and delineate potential therapeutic strategies, such as broadbased immunosuppression versus a more selective approach targeted against CD4 + T lymphocytes. The high efficacy of topical treatments (ie, inhalation) supports the notion that changes that are detectable in peripheral blood merely reflect a "spill-over" of local T-lymphocyte responses in the target organ. Conversely, the multiple systemic manifestations of allergy (such as allergic rhinitis and atopic dermatitis in atopic patients) support systemic therapeutic approaches. (J Allergy Clin Immunol 2000;106:S221-6.)
American Journal of Respiratory Cell and Molecular Biology, 2005
T lymphocytes modulate the pulmonary inflammatory response. The aim of this study was to evaluate the clonality within the interstitial lung and peripheral blood T cell receptor (TCR) repertoire in smokers. Interstitial T lymphocytes were isolated from surplus tissue of 16 patients (63 Ϯ 9 [Ϯ SD] yr old, 11 male) undergoing surgery due to lung cancer (n ϭ 15) or emphysema. TCR clonality was assessed by PCR amplification followed by spectratyping. Nearly all TCR of interstitial lung lymphocytes showed oligoclonal bands (CD4 ϩ subset 13/16 patients, 81%; CD8 ϩ 100%) indicating a specific differentiation. Peripheral blood T lymphocytes (PBL) TCR (especially CD4 ϩ) had less oligoclonal bands (CD4 ϩ 31%, CD8 ϩ 88%). Likewise, more oligoclonal bands were seen in lung TCR (total of 168 bands; 37 CD4 ϩ ; 131 CD8 ϩ), compared with 59 bands in PBL TCR (13 CD4 ϩ ; 46 CD8 ϩ). Intraindividual comparison revealed a more prominent difference in TCR oligoclonality between lung and blood in CD8 ϩ T cells (median of difference lung minus blood 5; interquartile range 1-10; P ϭ 0.002) compared with CD4 ϩ T cells (median 2, 0-3, P ϭ 0.039). Thus, TCR oligoclonality is preferentially found in the CD8 ϩ T cell subset, most distinctive in the lung. These findings indicate a specific interstitial T cell differentiation in response to local stimuli.
Clinical Immunology, 2001
The objective of this study was to identify diseaseassociated T cell subsets by characterizing the lung and blood T cell receptor (TCR) repertoires in allergic asthmatics before and after repeated low-dose allergen challenge. Peripheral blood lymphocyte (PBL) and bronchoalveolar lavage (BAL) samples were obtained from eight patients with allergic asthma before and after a period of repeated low-dose allergen inhalations. RT-PCR followed by Southern blot allowed the quantification of relative V gene segment usage. Thirteen healthy individuals served as controls at PBL level. PBL as well as BAL T cells of asthmatics displayed a higher usage of V3, V5.2, and V6.1-3 and a lower usage of V16, V18, and V19 compared to PBL of healthy controls. Interestingly, TCR V7 and V9 usage was significantly higher in BAL than in PBL in asthmatics before as well as after challenge. TCR repertoire alterations after allergen challenge differed between individuals, with relatively mild changes.
Journal of Allergy and Clinical Immunology, 1997
Background: In allergie subjeets with asthma, the migration of CD4 + T cells to the lungs in the hours after allergen exposure may contribute to allergic inflammation in the target organ. Objective: We studied allergen-specific T cells from the peripheral blond and lungs of allergie subjects with asthma at baseline and after allergen challenge. Methods: In each patient, blood samples were taken 10 minutes before and 24 hours after the inhalation of a major sensitizing allergen. In vitro proliferation of peripheral blood CD4 ÷ T cells specific for the same ailergen used in the in vivo challenge was assessed. In one patient two Dermatophagoldes pteronyssinus-specific T-cell clones (TCCs) were derived from peripheral blood, and their T-cell receptors were sequenced to determine their clonotypic determinants on the B chains. The T-cell receptor determinants of the allergenspecific TCCs were sought in blood and bronchoalveolar lavage samples taken from this patient. Results: We found that allergen inhalation is followed by a decrement in the specific pro|iferation of peripheral CD4+ T cells to the same allergen used for bronchial provocation. In one patient the clonotypic determinants of two allergen-specific TCCs diminished in the peripherai blood, whereas they were simultaneously expanded in the lower respiratory tract. Conclusion: Our data suggest that allergen-specific T cells are recruited from the peripheral biood to the bronchial lumen after allergen ehallenge.