Reversible Alterations in Immunoregulatory T Cells in Smoking: Analysis By Monoclonal Antibodies and Flow Cytometry

doi:10.1378/chest.82.5.526

Chest

Volume 82, Issue 5, November 1982, Pages 526-529

https://doi.org/10.1378/chest.82.5.526 Get rights and content

We characterized T-lymphocyte subsets in peripheral blood of smokers (N=60) and nonsmokers (N=35). Total T-lymphocytes and T cell subsets were similar to nonsmokers in light and moderate smokers. In heavy smokers, total OKT3⁺ cells were increased, the percentage of OKT4⁺ cells was decreased, and percentage and total number of OKT8⁺ cells were increased. The ratio of OKT4⁺ to OKT8⁺ lymphocytes was decreased in heavy smokers. The percentage of OKT8⁺ cells and the OKT4⁺/OKT8⁺ ratio returned to normal in heavy smokers six weeks after they stopped smoking. These findings suggest that cigarette smoking causes reversible alterations in immunoregulatory T cells.

Section snippets

METHODS

Our sample population consisted of 60 smokers (age range, 26 to 72; 26 women, 34 men) and 35 nonsmoking controls (age range, 22 to 71; 19 women, 16 men). No subject had immunodeficiency, took corticosteroids or immunosuppressives, or had serious illness or acute viral syndrome in the preceding two months. Normal subjects and smokers were comparable with regard to age and sex. We used two methods to classify smokers: (1) total smoking history: light (10 to 19 pack-years, N=17); moderate (20 to

RESULTS

Analyzing total smoking history, we found that WBCs were increased in all groups of smokers, but the percentage of lymphocytes was not different from normal subjects. Total lymphocyte count was elevated in heavy smokers due to the increase in WBCs. Results of T cell subset analysis are presented in Fig 1. Percentages of OKT3⁺ and OKT4⁺ cells were similar in all groups of smokers and normal subjects. Among smokers, the percentage of OKT4⁺ cells was significantly decreased in heavy smokers (41 ±

DISCUSSION

We have found alterations in T-lymphocyte subsets in heavy smoking. These abnormalities are at least partially restored to normal soon after smoking cessation. We confirmed prior reports that WBC is elevated in smokers regardless of the amount of smoking. This effect accounted for an increase in total lymphocyte count in heavy smokers.⁴

In normal subjects, the OKT3⁺ antibody reacts with circulating T cells which display mature T cell function.⁹ This antibody reacts with only about 90 percent of

ACKNOWLEDGMENTS

The authors thank Dr. R. B. Colvin for assistance; Dr. C. A. Hales, Dr. H. Kazemi, and Dr. H. Winn for comments; the American Cancer Society and the American Lung Association for allowing participation in their workshops; and Ms. Diane Bachiri for expert secretarial assistance.

REFERENCES (26)

CorberandJ et al.
Effect of tobacco smoking on the functions of polymorphonuclear leukocytes
Infect Immun
(1979)
GerardJW et al.
Immunoglobulin levels in smokers and non-smokers
Ann Allergy
(1980)
FersonM et al.
Low natural killer-cell activity and immunoglobulin levels associated with smoking in human subjects
Int J Cancer
(1979)
SilvermanNA et al.
In vitro lymphocyte reactivity and T-cell levels in chronic cigarette smokers
Clin Exp Immunol
(1975)
DanieleRP et al.
Lymphocyte studies in asymptomatic cigarette smokers
Am Rev Respir Dis
(1977)
HoffmanRA et al.
Simple and rapid determination of human T lymphocytes and their subclasses in peripheral blood
Proc Natl Acad Sci USA
(1980)
KungPC et al.
Functional and developmental compartments of human T-lymphocytes
Vox Sang
(1980)
BreardJ et al.
A monoclonal antibody reactive with human peripheral blood monocytes
J Immunol
(1980)
ReinherzEL et al.
A monoclonal antibody with selective reactivity with functionally mature human thymocytes and all peripheral human T cells
J Immunol
(1979)
ZarlingJM et al.
Monoclonal antibodies which distinguish between human NK cells and cytotoxic T-lymphocytes
Nature
(1981)

WarrGA et al.

Classification of bronchial lymphocytes from nonsmokers and smokers

Am Rev Respir Dis

(1976)

ThomasY et al.

Functional analysis of human T cell subsets defined by monoclonal autibodies: I. Collaborative T-T interactions in the immunoregulation of B cell differentiation

J Immunol

(1980)

ReinherzEL et al.

Subpopulations of the T4+ inducer T cell subset in man: evidence for an amplifier population preferentially expressing Ia antigen upon activation

J Immunol

(1981)

Cited by (208)

Coronavirus Disease 2019 and Smoking: How and Why We Implemented a Tobacco Treatment Campaign
2020, Chest
Citation Excerpt :
Cigarette smoke has been shown to up-regulate inflammation through activation of nuclear factor kappa-light-chain-enhancer of activated B cells, tumor necrosis factor-α, IL-1beta, and neutrophils19,20 and to down-regulate successful immune function.21-24 This effect is proportional to an increase in smoking and does not subside immediately after discontinuation of use.25-27 Patients with SARS-CoV-2 have been shown to have elevated levels of the inflammatory cytokines tumor necrosis factor-α, IL-2R, and IL-6 on presentation, and the virus causes lymphocytopenia.28,29
Smoking is associated with one of five deaths in the United States. Multimodality tobacco treatment increases rates of successful cessation by at least 20%. The coronavirus disease 2019 pandemic has put a halt to many inpatient and outpatient medical visits that have been deemed nonessential, including tobacco treatment. The transition to telehealth has been wrought with challenges. Although data on the association between coronavirus disease 2019 and tobacco products are mixed, the overall health consequences of tobacco point towards increased risk of morbidity and death that is associated with the virus. This leaves smoking as one of the few readily modifiable risk factors in an environment understandably not set up to prioritize cessation. A military health facility on Fort Eustis in Virginia runs a successful tobacco treatment program and adapted it to pandemic times. This article describes the process and lessons learned from this initiative. The model is applicable and scalable to government and civilian health centers as health care adapts to a new normal.
Radiation-induced lung toxicity predictors: Retrospective analysis of 90 patients treated with stereotactic body radiation therapy for stage I non-small-cell lung carcinoma
2020, Cancer/Radiotherapie
The main complication after hypofractionated radiotherapy for lung carcinoma is radiation-induced lung toxicity, which can be divided into radiation pneumonitis (acute toxicity, occurring within 6 months) and lung fibrosis (late toxicity, occurring after 6 months). The literature describes several predictive factors related to the patient, to the tumor (volume, central location), to the dosimetry and to biological factors.
This study is a retrospective analysis of 90 patients treated with stereotactic body irradiation for stage I non-small-cell lung carcinoma between December 2010 and May 2015.
Radiation pneumonitis was observed in 61.5% of the patients who were mainly asymptomatic (34%). Chronic obstructive pulmonary disease was not predictive of radiation pneumonitis, whereas active smoking was protective. Centrally located tumors were not more likely to result in this complication if the radiation schedule utilized adapted fractionation. In our study, no predictive factor was identified. Whereas the mean lung dose was a predictive factor in 3D radiotherapy, the lung volume irradiated at high doses seemed to be involved in the pathogenesis after hypofractionated radiotherapy.
The discovery of predictive factors for radiation pneumonitis is difficult due to the rarity of this complication, especially with an 8 × 7.5 Gy schedule. Radiation pneumonitis seems to be correlated with the volume irradiated at high doses, which is in contrast to the known knowledge about the organs in parallel. This finding leads us to raise the hypothesis that vessel damage, organs in series, occurring during hypofractionated radiotherapy could be responsible for this toxicity.
La principale complication après radiothérapie hypofractionnée dans le cadre des carcinomes bronchopulmonaires est la toxicité pulmonaire radio-induite, qui peut être divisée en pneumopathie radique (toxicité aiguë survenant dans les 6 mois) et en fibrose pulmonaire (toxicité tardive survenant après 6 mois). La littérature décrit plusieurs facteurs prédictifs, liés au patient, à la tumeur (volume, emplacement central), à la dosimétrie et des facteurs biologiques.
Cette étude est une analyse rétrospective de 90 patients traités par irradiation stéréotaxique pour un carcinome bronchopulmonaire non à petites cellules de stade I entre décembre 2010 et mai 2015.
Une pneumopathie radique radiologique a été observée chez 61,5 % des patients, principalement asymptomatiques (34 %). Un antécédent de bronchite chronique obstructive n’était pas prédictif de pneumopathie radique, alors que le tabagisme actif était un facteur protecteur. Les tumeurs de localisation centrales n’étaient pas plus susceptibles de contracter cette complication dès lors que le fractionnement était adapté. Dans notre étude, aucun facteur prédictif n’a été identifié. Alors que la dose pulmonaire moyenne est un facteur prédictif en radiothérapie 3D, le volume pulmonaire irradié à fortes doses semble être impliqué dans la pathogenèse après la radiothérapie hypofractionnée.
La découverte de facteurs prédictifs de pneumopathie radique est rendue difficile par la rareté de cette complication, en particulier avec le schéma 8 × 7,5 Gy. Cela semble être corrélé au volume irradié à fortes doses, ce qui est contradictoire pour des organes en parallèle. Cette découverte nous amène à émettre l’hypothèse selon laquelle les dommages aux structures vasculaires, organes en série, survenant au cours de la radiothérapie hypofractionnée, pourraient être responsables de cette toxicité.
Smoking, smoking cessation and Crohn's disease
2016, Presse Medicale
Le tabagisme dont la prévalence est plus élevée chez les patients atteints de maladie de Crohn (MC) aggrave son évolution. En revanche, la recto-colite ulcéro-hémorragique affecte essentiellement des non- ou ex-fumeurs ; le tabagisme peut améliorer le cours de la maladie.
Revue systématique de la littérature sur les données concernant la relation entre tabagisme, sevrage tabagique et maladie de Crohn.
Medline sur la période 1980–2015 avec pour mots-clés « Crohn's disease » ou « inflammatory bowel disease » et « smoking » ou « smoking cessation » et pour limites « Title/Abstract » ; les langues retenues étaient l’anglais et le français.
Parmi 1315 articles, 168 résumés sélectionnés ont donné lieu à une double lecture aboutissant à retenir 69 études (cas-témoins, rétrospectives, prospectives, revues ou méta-analyses). Les données ont été extraites à partir d’une grille de lecture.
Le tabagisme augmente le risque de complications, récidives et de recours aux traitements chirurgical, corticoïdes ou immunosuppresseurs chez le patient atteint de MC. Ces effets délétères sont plus fréquents chez la femme. L’arrêt de la consommation de tabac améliore l’évolution de la maladie et représente un élément essentiel de sa prise en charge.
Hétérogénéité des études rassemblées selon le type, les caractéristiques des populations, la définition du statut tabagique et la validation de l’arrêt du tabac.
Les fumeurs atteints de MC doivent être systématiquement sensibilisés aux effets néfastes du tabagisme, aux bénéfices de l’abstinence et aidés à s’arrêter de fumer.
Smoking whose prevalence is higher in patients with Crohn's disease (CD) worsens its evolution. Ulcerative colitis mostly affect non- or ex-smokers; smoking may improve the course of the disease.
Systematic literature review of data on the relationship between smoking, smoking cessation and Crohn’disease.
Medline, on the period 1980–2015 with the keywords “Crohn's disease” or “inflammatory bowel disease” and “smoking” or “smoking cessation”; limits “Title/Abstract”; the selected languages were English or French.
Among 1315 articles, 168 abstracts have given rise to a dual reading to select 69 studies (case-control, retrospective, reviews or meta-analysis). Data were extracted using a reading gate.
Smoking increases the risk of complications, recurrences and resort of surgery, corticosteroids or immunosuppressants. These deleterious effects are more common in women. Stopping smoking improves the course of the disease and represents an essential component of its management.
Heterogeneity of the studies collected according to the type, population characteristics, definition of smoking status and the validation of smoking cessation.
Smokers suffering from CD must routinely be made aware of the disadvantages of smoking, benefits of abstinence and helped to quit smoking.
Nondosimetric Risk Factors for Radiation-Induced Lung Toxicity
2015, Seminars in Radiation Oncology
The decision to administer a radical course of radiotherapy (RT) is largely influenced by the dose-volume metrics of the treatment plan, but what are the patient-related and other factors that may independently increase the risk of radiation lung toxicity? Poor pulmonary function has been regarded as a risk factor and a relative contraindication for patients undergoing radical RT, but recent evidence suggests that patients with poor spirometry results may tolerate conventional or high-dose RT as well as, if not better than, patients with normal function. However, caution may need to be exercised in patients with underlying interstitial pulmonary fibrosis. Furthermore, there is emerging evidence of molecular markers of increased risk of toxicity. This review discusses patient-related risk factors other than dosimetry for radiation lung toxicity.
Determination of lymphocyte subset reference ranges in peripheral blood of healthy adults by a dual-platform flow cytometry method
2015, Immunology Letters
Citation Excerpt :
Samples that had clots, hemolysis, or positive serologic test results (HBsAg, anti-HBc, anti-HCV, anti-HTLV-I/II, syphilis, HIV-I/II antigen, and Trypanosoma cruzi antibody) were excluded from the study. Previous studies had shown that smokers have a significant alteration in some lymphocyte subset counts [6,24–27], consequently, smokers were not included in this research. Samples were processed by a dual-platform method [8] that used the flow cytometer FACSCanto II (BD Biosciences, USA) for relative value counts and the Sysmex XE-2100D (Sysmex Corporation, Japan) hematology cell analyzer to enumerate absolute lymphocyte counts.
Flow cytometry has emerged as a useful screening approach to evaluate whether specific cell populations are present or absent. Previous studies have shown different reference ranges in several countries. The aim of this study was to determine reference ranges of lymphocyte subsets in peripheral blood by flow cytometric method in Brazilian adults. In this study, relative and absolute reference ranges of lymphocyte subsets were: CD3+: 51.3–83.5%, 718–2494 cells/μl; CD4+: 24.4–54.2%, 456–1492 cells/μl; CD8+: 12.8–40.2%, 272–1144 cells/μl; CD4+CD8+: double-positive 0.01–3.6%, 2–88 cells/μl; TCR γδ: 1.0–15.9%, 19–345 cells/μl; CD3+CD4−CD8−: 1.2–13.3%, 28–292 cells/μl; TCR αβ+: 44.3–77.0%, 855–2384 cells/μl; CD4/CD8 ratio: 0.68–3.61; CD19+: 6.3–20.8%, 112–622 cells/μl; mature NK cells: 3.1–27.4%, 70–745 cells/μl; immature NK cells: 0.08–1.1%, 1–23 cells/μl; total NK cells: 3.7–28.5%, 82–760 cells/μl; and NKT cells: 0.9–21.4%, 18–488 cells/μl. Comparison with other studies showed differences among some of them. This suggests that there are differences among lymphocyte subsets in the worldwide population and also it is important to determine reference ranges in different populations in order to better assess and monitor patients.
Association of cigarette smoking with a past history and incidence of herpes zoster in the general Japanese population: The SHEZ Study
2017, Epidemiology and Infection

View all citing articles on Scopus

Supported in part by Biomedical Research support grant 78-10; Young Pulmonary Investigator award R23H124581; and NIH Training Grant HL07345.

Presented in part at the annual meeting of the Eastern Section, American Thoracic Society, Hanover, NH, Sept. 25, 1981.

Manuscript received April 5; revision accepted June 15.

^*: Pulmonary Unit, General Medical Services, Massachusetts General Hospital, and Department of Medicine, Harvard Medical School, Boston.

^{^†}: Ortho Pharmaceuticals, Raritan, NJ.

View full text

Chest

clinical investigationsReversible Alterations in Immunoregulatory T Cells in Smoking: Analysis By Monoclonal Antibodies and Flow Cytometry

Section snippets

METHODS

RESULTS

DISCUSSION

ACKNOWLEDGMENTS

Effect of tobacco smoking on the functions of polymorphonuclear leukocytes

Infect Immun

Immunoglobulin levels in smokers and non-smokers

Ann Allergy

Low natural killer-cell activity and immunoglobulin levels associated with smoking in human subjects

Int J Cancer

In vitro lymphocyte reactivity and T-cell levels in chronic cigarette smokers

Clin Exp Immunol

Lymphocyte studies in asymptomatic cigarette smokers

Am Rev Respir Dis

Simple and rapid determination of human T lymphocytes and their subclasses in peripheral blood

Proc Natl Acad Sci USA

Functional and developmental compartments of human T-lymphocytes

Vox Sang

A monoclonal antibody reactive with human peripheral blood monocytes

J Immunol

A monoclonal antibody with selective reactivity with functionally mature human thymocytes and all peripheral human T cells

J Immunol

Monoclonal antibodies which distinguish between human NK cells and cytotoxic T-lymphocytes

Nature

Classification of bronchial lymphocytes from nonsmokers and smokers

Am Rev Respir Dis

Functional analysis of human T cell subsets defined by monoclonal autibodies: I. Collaborative T-T interactions in the immunoregulation of B cell differentiation

J Immunol

Subpopulations of the T4+ inducer T cell subset in man: evidence for an amplifier population preferentially expressing Ia antigen upon activation

J Immunol

clinical investigations
Reversible Alterations in Immunoregulatory T Cells in Smoking: Analysis By Monoclonal Antibodies and Flow Cytometry