T-lymphocytes that accumulate in the lung in sarcoidosis have evidence of recent stimulation of the T-cell antigen receptor

R. M. Du Bois, M. Kirby, B. Balbi, C. Saltini, Ronald Crystal

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Sarcoidosis, a granulomatous disease of unknown etiology, is characterized at sites of disease such as the lung by the accumulation of large numbers of T-lymphocytes. To differentiate whether the T-cells accumulate in organs nonspecifically (e.g., through chemotaxis or tumorlike proliferation) or more specifically through an antigen-driven ordered immune response, the present study capitalized on the knowledge that specific antigen stimulation of T- cells requires antigen interactions with the T-cell antigen receptor (TCR), resulting in a decrease in the number of surface TCR and a concomitant increase in TCR mRNA levels, i.e., if lung T-cell accumulation in pulmonary sarcoid results from an ordered immune response, lung, but not blood, T-cells should demonstrate evidence of recent triggering of the αβ receptor, the most abundant type of TCR. The surface density of T-cell surface αβ TCR expression was evaluated by flow cytometry with an anti-αβ antibody and TCR β-chain mRNA transcript number quantified by in situ hybridization with 35S-labeled antisense and sense cRNA probes. Control studies utilizing normal blood T-lymphocytes stimulated with the anti-CD3 monoclonal antibody, OKT3, in the presence of autologous monocytes, demonstrated the expected down-regulation of surface αβ TCR expression and increased β-chain mRNA transcript number. When lung and blood T-cells of patients with pulmonary sarcoidosis were compared immediately upon recovery (i.e., without in vitro stimulation), the lung T-cells of 10 of 10 subjects demonstrated a decreased surface density of αβ TCR compared with their autologous blood T-cells. Furthermore, lung T-cells of eight of nine of these subjects exhibited an increase in β-chain mRNA transcripts compared with their autologous blood T- lymphocytes. Together, these observations are consistent with the concept that lung, but not blood, T-cells in active pulmonary sarcoidosis have recently been activated through a mechanism that modulates T-cell surface antigen receptor. This process is likely antigen-driven although activation via other ligand-receptor bindings may occur and have not been directly excluded in this study. Overall, these data give support to the hypothesis that the T-cells accumulate in the lung in pulmonary sarcoid in response to persistent antigenic stimulation.

Original languageEnglish
Pages (from-to)1205-1211
Number of pages7
JournalAmerican Review of Respiratory Disease
Volume145
Issue number5
DOIs
Publication statusPublished - 1 Jan 1992
Externally publishedYes

Fingerprint

Sarcoidosis
T-Cell Antigen Receptor
T-Lymphocytes
Lung
Surface Antigens
Blood Cells
Pulmonary Sarcoidosis
Antigens
Messenger RNA
Muromonab-CD3
Complementary RNA
Cell Surface Receptors
Chemotaxis
In Situ Hybridization
Monocytes
Anti-Idiotypic Antibodies
Flow Cytometry
Down-Regulation

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

T-lymphocytes that accumulate in the lung in sarcoidosis have evidence of recent stimulation of the T-cell antigen receptor. / Du Bois, R. M.; Kirby, M.; Balbi, B.; Saltini, C.; Crystal, Ronald.

In: American Review of Respiratory Disease, Vol. 145, No. 5, 01.01.1992, p. 1205-1211.

Research output: Contribution to journalArticle

@article{1fe6e10eadeb4f81b492f4dc6966b483,
title = "T-lymphocytes that accumulate in the lung in sarcoidosis have evidence of recent stimulation of the T-cell antigen receptor",
abstract = "Sarcoidosis, a granulomatous disease of unknown etiology, is characterized at sites of disease such as the lung by the accumulation of large numbers of T-lymphocytes. To differentiate whether the T-cells accumulate in organs nonspecifically (e.g., through chemotaxis or tumorlike proliferation) or more specifically through an antigen-driven ordered immune response, the present study capitalized on the knowledge that specific antigen stimulation of T- cells requires antigen interactions with the T-cell antigen receptor (TCR), resulting in a decrease in the number of surface TCR and a concomitant increase in TCR mRNA levels, i.e., if lung T-cell accumulation in pulmonary sarcoid results from an ordered immune response, lung, but not blood, T-cells should demonstrate evidence of recent triggering of the αβ receptor, the most abundant type of TCR. The surface density of T-cell surface αβ TCR expression was evaluated by flow cytometry with an anti-αβ antibody and TCR β-chain mRNA transcript number quantified by in situ hybridization with 35S-labeled antisense and sense cRNA probes. Control studies utilizing normal blood T-lymphocytes stimulated with the anti-CD3 monoclonal antibody, OKT3, in the presence of autologous monocytes, demonstrated the expected down-regulation of surface αβ TCR expression and increased β-chain mRNA transcript number. When lung and blood T-cells of patients with pulmonary sarcoidosis were compared immediately upon recovery (i.e., without in vitro stimulation), the lung T-cells of 10 of 10 subjects demonstrated a decreased surface density of αβ TCR compared with their autologous blood T-cells. Furthermore, lung T-cells of eight of nine of these subjects exhibited an increase in β-chain mRNA transcripts compared with their autologous blood T- lymphocytes. Together, these observations are consistent with the concept that lung, but not blood, T-cells in active pulmonary sarcoidosis have recently been activated through a mechanism that modulates T-cell surface antigen receptor. This process is likely antigen-driven although activation via other ligand-receptor bindings may occur and have not been directly excluded in this study. Overall, these data give support to the hypothesis that the T-cells accumulate in the lung in pulmonary sarcoid in response to persistent antigenic stimulation.",
author = "{Du Bois}, {R. M.} and M. Kirby and B. Balbi and C. Saltini and Ronald Crystal",
year = "1992",
month = "1",
day = "1",
doi = "10.1164/ajrccm/145.5.1205",
language = "English",
volume = "145",
pages = "1205--1211",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "5",

}

TY - JOUR

T1 - T-lymphocytes that accumulate in the lung in sarcoidosis have evidence of recent stimulation of the T-cell antigen receptor

AU - Du Bois, R. M.

AU - Kirby, M.

AU - Balbi, B.

AU - Saltini, C.

AU - Crystal, Ronald

PY - 1992/1/1

Y1 - 1992/1/1

N2 - Sarcoidosis, a granulomatous disease of unknown etiology, is characterized at sites of disease such as the lung by the accumulation of large numbers of T-lymphocytes. To differentiate whether the T-cells accumulate in organs nonspecifically (e.g., through chemotaxis or tumorlike proliferation) or more specifically through an antigen-driven ordered immune response, the present study capitalized on the knowledge that specific antigen stimulation of T- cells requires antigen interactions with the T-cell antigen receptor (TCR), resulting in a decrease in the number of surface TCR and a concomitant increase in TCR mRNA levels, i.e., if lung T-cell accumulation in pulmonary sarcoid results from an ordered immune response, lung, but not blood, T-cells should demonstrate evidence of recent triggering of the αβ receptor, the most abundant type of TCR. The surface density of T-cell surface αβ TCR expression was evaluated by flow cytometry with an anti-αβ antibody and TCR β-chain mRNA transcript number quantified by in situ hybridization with 35S-labeled antisense and sense cRNA probes. Control studies utilizing normal blood T-lymphocytes stimulated with the anti-CD3 monoclonal antibody, OKT3, in the presence of autologous monocytes, demonstrated the expected down-regulation of surface αβ TCR expression and increased β-chain mRNA transcript number. When lung and blood T-cells of patients with pulmonary sarcoidosis were compared immediately upon recovery (i.e., without in vitro stimulation), the lung T-cells of 10 of 10 subjects demonstrated a decreased surface density of αβ TCR compared with their autologous blood T-cells. Furthermore, lung T-cells of eight of nine of these subjects exhibited an increase in β-chain mRNA transcripts compared with their autologous blood T- lymphocytes. Together, these observations are consistent with the concept that lung, but not blood, T-cells in active pulmonary sarcoidosis have recently been activated through a mechanism that modulates T-cell surface antigen receptor. This process is likely antigen-driven although activation via other ligand-receptor bindings may occur and have not been directly excluded in this study. Overall, these data give support to the hypothesis that the T-cells accumulate in the lung in pulmonary sarcoid in response to persistent antigenic stimulation.

AB - Sarcoidosis, a granulomatous disease of unknown etiology, is characterized at sites of disease such as the lung by the accumulation of large numbers of T-lymphocytes. To differentiate whether the T-cells accumulate in organs nonspecifically (e.g., through chemotaxis or tumorlike proliferation) or more specifically through an antigen-driven ordered immune response, the present study capitalized on the knowledge that specific antigen stimulation of T- cells requires antigen interactions with the T-cell antigen receptor (TCR), resulting in a decrease in the number of surface TCR and a concomitant increase in TCR mRNA levels, i.e., if lung T-cell accumulation in pulmonary sarcoid results from an ordered immune response, lung, but not blood, T-cells should demonstrate evidence of recent triggering of the αβ receptor, the most abundant type of TCR. The surface density of T-cell surface αβ TCR expression was evaluated by flow cytometry with an anti-αβ antibody and TCR β-chain mRNA transcript number quantified by in situ hybridization with 35S-labeled antisense and sense cRNA probes. Control studies utilizing normal blood T-lymphocytes stimulated with the anti-CD3 monoclonal antibody, OKT3, in the presence of autologous monocytes, demonstrated the expected down-regulation of surface αβ TCR expression and increased β-chain mRNA transcript number. When lung and blood T-cells of patients with pulmonary sarcoidosis were compared immediately upon recovery (i.e., without in vitro stimulation), the lung T-cells of 10 of 10 subjects demonstrated a decreased surface density of αβ TCR compared with their autologous blood T-cells. Furthermore, lung T-cells of eight of nine of these subjects exhibited an increase in β-chain mRNA transcripts compared with their autologous blood T- lymphocytes. Together, these observations are consistent with the concept that lung, but not blood, T-cells in active pulmonary sarcoidosis have recently been activated through a mechanism that modulates T-cell surface antigen receptor. This process is likely antigen-driven although activation via other ligand-receptor bindings may occur and have not been directly excluded in this study. Overall, these data give support to the hypothesis that the T-cells accumulate in the lung in pulmonary sarcoid in response to persistent antigenic stimulation.

UR - http://www.scopus.com/inward/record.url?scp=0026802079&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026802079&partnerID=8YFLogxK

U2 - 10.1164/ajrccm/145.5.1205

DO - 10.1164/ajrccm/145.5.1205

M3 - Article

C2 - 1533998

AN - SCOPUS:0026802079

VL - 145

SP - 1205

EP - 1211

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 5

ER -