Bias toward use of a specific T cell receptor β-chain variable region in a subgroup of individuals with sarcoidosis

D. R. Moller, K. Konishi, M. Kirby, B. Balbi, Ronald Crystal

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

To evaluate the concept that biases in the usage of T cell antigen receptor β variable (V) regions may be manifested in T lymphocytes that accumulate in nonmalignant, T cell-mediated human disorders, a V(β)8-specific antibody (anti-T(i3A), 5REX9H5) was used to evaluate lung and blood T cells in pulmonary sarcoidosis, a chronic granulomatous disorder of unknown etiology. Whereas normal patients had <5% T(i3A+) lung (n = 7) and/or blood (n = 9) lymphocytes, strikingly, a subgroup (8 of 21) with active pulmonary sarcoidosis had >7% T(i3A+) lung and/or blood T cells and a higher proportion of T(i3A+) lymphocytes in the lung compared with blood. Dual-color flow cytometry demonstrated compartmentalization of T(i3A+) CD4+ lymphocytes to lung and T(i3A+) CD8+ lymphocytes to blood. Analysis with a 32P-labeled V(β)8 probe revealed that sarcoid lung T lymphocytes contained higher amounts of V(β)8+ mRNA than autologous blood T cells. However, Southern analysis of sarcoid lung and blood T cell DNA demonstrated no evidence of clonal rearrangements of V(β)8 genes. These observations demonstrate a clear bias toward the use of at least one V(β) region in sarcoidosis, and suggests T cells accumulate secondary to external selective pressure, rather than in a random polyclonal fashion or by clonal expansion of one or few T cell clones.

Original languageEnglish
Pages (from-to)1183-1191
Number of pages9
JournalJournal of Clinical Investigation
Volume82
Issue number4
Publication statusPublished - 1 Jan 1988
Externally publishedYes

Fingerprint

Sarcoidosis
T-Cell Antigen Receptor
T-Lymphocytes
Lung
Blood Cells
Lymphocytes
Pulmonary Sarcoidosis
Flow Cytometry
Clone Cells
Color
Messenger RNA
Antibodies

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Bias toward use of a specific T cell receptor β-chain variable region in a subgroup of individuals with sarcoidosis. / Moller, D. R.; Konishi, K.; Kirby, M.; Balbi, B.; Crystal, Ronald.

In: Journal of Clinical Investigation, Vol. 82, No. 4, 01.01.1988, p. 1183-1191.

Research output: Contribution to journalArticle

@article{448921f3bcca49bb94e04b30f616e76c,
title = "Bias toward use of a specific T cell receptor β-chain variable region in a subgroup of individuals with sarcoidosis",
abstract = "To evaluate the concept that biases in the usage of T cell antigen receptor β variable (V) regions may be manifested in T lymphocytes that accumulate in nonmalignant, T cell-mediated human disorders, a V(β)8-specific antibody (anti-T(i3A), 5REX9H5) was used to evaluate lung and blood T cells in pulmonary sarcoidosis, a chronic granulomatous disorder of unknown etiology. Whereas normal patients had <5{\%} T(i3A+) lung (n = 7) and/or blood (n = 9) lymphocytes, strikingly, a subgroup (8 of 21) with active pulmonary sarcoidosis had >7{\%} T(i3A+) lung and/or blood T cells and a higher proportion of T(i3A+) lymphocytes in the lung compared with blood. Dual-color flow cytometry demonstrated compartmentalization of T(i3A+) CD4+ lymphocytes to lung and T(i3A+) CD8+ lymphocytes to blood. Analysis with a 32P-labeled V(β)8 probe revealed that sarcoid lung T lymphocytes contained higher amounts of V(β)8+ mRNA than autologous blood T cells. However, Southern analysis of sarcoid lung and blood T cell DNA demonstrated no evidence of clonal rearrangements of V(β)8 genes. These observations demonstrate a clear bias toward the use of at least one V(β) region in sarcoidosis, and suggests T cells accumulate secondary to external selective pressure, rather than in a random polyclonal fashion or by clonal expansion of one or few T cell clones.",
author = "Moller, {D. R.} and K. Konishi and M. Kirby and B. Balbi and Ronald Crystal",
year = "1988",
month = "1",
day = "1",
language = "English",
volume = "82",
pages = "1183--1191",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "4",

}

TY - JOUR

T1 - Bias toward use of a specific T cell receptor β-chain variable region in a subgroup of individuals with sarcoidosis

AU - Moller, D. R.

AU - Konishi, K.

AU - Kirby, M.

AU - Balbi, B.

AU - Crystal, Ronald

PY - 1988/1/1

Y1 - 1988/1/1

N2 - To evaluate the concept that biases in the usage of T cell antigen receptor β variable (V) regions may be manifested in T lymphocytes that accumulate in nonmalignant, T cell-mediated human disorders, a V(β)8-specific antibody (anti-T(i3A), 5REX9H5) was used to evaluate lung and blood T cells in pulmonary sarcoidosis, a chronic granulomatous disorder of unknown etiology. Whereas normal patients had <5% T(i3A+) lung (n = 7) and/or blood (n = 9) lymphocytes, strikingly, a subgroup (8 of 21) with active pulmonary sarcoidosis had >7% T(i3A+) lung and/or blood T cells and a higher proportion of T(i3A+) lymphocytes in the lung compared with blood. Dual-color flow cytometry demonstrated compartmentalization of T(i3A+) CD4+ lymphocytes to lung and T(i3A+) CD8+ lymphocytes to blood. Analysis with a 32P-labeled V(β)8 probe revealed that sarcoid lung T lymphocytes contained higher amounts of V(β)8+ mRNA than autologous blood T cells. However, Southern analysis of sarcoid lung and blood T cell DNA demonstrated no evidence of clonal rearrangements of V(β)8 genes. These observations demonstrate a clear bias toward the use of at least one V(β) region in sarcoidosis, and suggests T cells accumulate secondary to external selective pressure, rather than in a random polyclonal fashion or by clonal expansion of one or few T cell clones.

AB - To evaluate the concept that biases in the usage of T cell antigen receptor β variable (V) regions may be manifested in T lymphocytes that accumulate in nonmalignant, T cell-mediated human disorders, a V(β)8-specific antibody (anti-T(i3A), 5REX9H5) was used to evaluate lung and blood T cells in pulmonary sarcoidosis, a chronic granulomatous disorder of unknown etiology. Whereas normal patients had <5% T(i3A+) lung (n = 7) and/or blood (n = 9) lymphocytes, strikingly, a subgroup (8 of 21) with active pulmonary sarcoidosis had >7% T(i3A+) lung and/or blood T cells and a higher proportion of T(i3A+) lymphocytes in the lung compared with blood. Dual-color flow cytometry demonstrated compartmentalization of T(i3A+) CD4+ lymphocytes to lung and T(i3A+) CD8+ lymphocytes to blood. Analysis with a 32P-labeled V(β)8 probe revealed that sarcoid lung T lymphocytes contained higher amounts of V(β)8+ mRNA than autologous blood T cells. However, Southern analysis of sarcoid lung and blood T cell DNA demonstrated no evidence of clonal rearrangements of V(β)8 genes. These observations demonstrate a clear bias toward the use of at least one V(β) region in sarcoidosis, and suggests T cells accumulate secondary to external selective pressure, rather than in a random polyclonal fashion or by clonal expansion of one or few T cell clones.

UR - http://www.scopus.com/inward/record.url?scp=0023717339&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023717339&partnerID=8YFLogxK

M3 - Article

C2 - 2459159

AN - SCOPUS:0023717339

VL - 82

SP - 1183

EP - 1191

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 4

ER -