Development and characterization of desmoglein-3 specific T cells from patients with pemphigus vulgaris

Mong Shang Lin, Sue J. Swartz, Argelia Lopez, Xiang Ding, Marcelo A. Fernandez-Vina, Peter Stastny, Janet A. Fairley, Luis A. Diaz

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

Pemphigus vulgaris (PV) is a cutaneous autoimmune disease characterized by blister formation in the suprabasilar layers of skin and mucosae and anti- desmoglein-3 (Dsg3) autoantibodies bound to the surface of lesional keratinocytes and circulating in the serum of patients. This disease can be reproduced in neonatal mice by passive transfer of patients' IgG, indicating that humoral immunity plays an important role in the pathogenesis of PV. Currently, the role of T lymphocytes in the development of PV is not clear. Here, we report that three immunoreactive segments of the ectodomain of Dsg3 specifically induced proliferation of T cells from PV patients. We found that T lymphocytes from 13 out of 14 patients responded to at least one of three Dsg3 peptides. T cells from controls and other patient groups did not respond to these Dsg3 peptides. The major T cell population stimulated by these Dsg3 peptides was CD4 positive. Dsg3-specific T cell lines and clones were developed and were shown to express a CD4 positive memory T cell phenotype. Upon stimulation, these cell lines and clones secreted a Th2-like cytokine profile. The Dsg3 responses of these T cells were restricted to HLA-DR, and not -DQ and -DP, of the major histocompatibility complex. This information will help to elucidate the cellular immune abnormalities leading to production of pathogenic IgG autoantibodies in patients with PV.

Original languageEnglish (US)
Pages (from-to)31-40
Number of pages10
JournalJournal of Clinical Investigation
Volume99
Issue number1
StatePublished - Jan 1 1997

Fingerprint

Desmoglein 3
Pemphigus
T-Lymphocytes
Autoantibodies
Peptides
Clone Cells
Immunoglobulin G
Patient Transfer
Cell Line
HLA-DR Antigens
Blister
Humoral Immunity
Major Histocompatibility Complex
Keratinocytes
Skin Diseases
Autoimmune Diseases
Mucous Membrane
Cytokines
Phenotype

Keywords

  • cytokines
  • desmoglein-3
  • MHC II restriction
  • pemphigus vulgaris
  • T lymphocytes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Lin, M. S., Swartz, S. J., Lopez, A., Ding, X., Fernandez-Vina, M. A., Stastny, P., ... Diaz, L. A. (1997). Development and characterization of desmoglein-3 specific T cells from patients with pemphigus vulgaris. Journal of Clinical Investigation, 99(1), 31-40.

Development and characterization of desmoglein-3 specific T cells from patients with pemphigus vulgaris. / Lin, Mong Shang; Swartz, Sue J.; Lopez, Argelia; Ding, Xiang; Fernandez-Vina, Marcelo A.; Stastny, Peter; Fairley, Janet A.; Diaz, Luis A.

In: Journal of Clinical Investigation, Vol. 99, No. 1, 01.01.1997, p. 31-40.

Research output: Contribution to journalArticle

Lin, MS, Swartz, SJ, Lopez, A, Ding, X, Fernandez-Vina, MA, Stastny, P, Fairley, JA & Diaz, LA 1997, 'Development and characterization of desmoglein-3 specific T cells from patients with pemphigus vulgaris', Journal of Clinical Investigation, vol. 99, no. 1, pp. 31-40.
Lin MS, Swartz SJ, Lopez A, Ding X, Fernandez-Vina MA, Stastny P et al. Development and characterization of desmoglein-3 specific T cells from patients with pemphigus vulgaris. Journal of Clinical Investigation. 1997 Jan 1;99(1):31-40.
Lin, Mong Shang ; Swartz, Sue J. ; Lopez, Argelia ; Ding, Xiang ; Fernandez-Vina, Marcelo A. ; Stastny, Peter ; Fairley, Janet A. ; Diaz, Luis A. / Development and characterization of desmoglein-3 specific T cells from patients with pemphigus vulgaris. In: Journal of Clinical Investigation. 1997 ; Vol. 99, No. 1. pp. 31-40.
@article{6888657104c44b07b991c968d5899ea4,
title = "Development and characterization of desmoglein-3 specific T cells from patients with pemphigus vulgaris",
abstract = "Pemphigus vulgaris (PV) is a cutaneous autoimmune disease characterized by blister formation in the suprabasilar layers of skin and mucosae and anti- desmoglein-3 (Dsg3) autoantibodies bound to the surface of lesional keratinocytes and circulating in the serum of patients. This disease can be reproduced in neonatal mice by passive transfer of patients' IgG, indicating that humoral immunity plays an important role in the pathogenesis of PV. Currently, the role of T lymphocytes in the development of PV is not clear. Here, we report that three immunoreactive segments of the ectodomain of Dsg3 specifically induced proliferation of T cells from PV patients. We found that T lymphocytes from 13 out of 14 patients responded to at least one of three Dsg3 peptides. T cells from controls and other patient groups did not respond to these Dsg3 peptides. The major T cell population stimulated by these Dsg3 peptides was CD4 positive. Dsg3-specific T cell lines and clones were developed and were shown to express a CD4 positive memory T cell phenotype. Upon stimulation, these cell lines and clones secreted a Th2-like cytokine profile. The Dsg3 responses of these T cells were restricted to HLA-DR, and not -DQ and -DP, of the major histocompatibility complex. This information will help to elucidate the cellular immune abnormalities leading to production of pathogenic IgG autoantibodies in patients with PV.",
keywords = "cytokines, desmoglein-3, MHC II restriction, pemphigus vulgaris, T lymphocytes",
author = "Lin, {Mong Shang} and Swartz, {Sue J.} and Argelia Lopez and Xiang Ding and Fernandez-Vina, {Marcelo A.} and Peter Stastny and Fairley, {Janet A.} and Diaz, {Luis A.}",
year = "1997",
month = "1",
day = "1",
language = "English (US)",
volume = "99",
pages = "31--40",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "1",

}

TY - JOUR

T1 - Development and characterization of desmoglein-3 specific T cells from patients with pemphigus vulgaris

AU - Lin, Mong Shang

AU - Swartz, Sue J.

AU - Lopez, Argelia

AU - Ding, Xiang

AU - Fernandez-Vina, Marcelo A.

AU - Stastny, Peter

AU - Fairley, Janet A.

AU - Diaz, Luis A.

PY - 1997/1/1

Y1 - 1997/1/1

N2 - Pemphigus vulgaris (PV) is a cutaneous autoimmune disease characterized by blister formation in the suprabasilar layers of skin and mucosae and anti- desmoglein-3 (Dsg3) autoantibodies bound to the surface of lesional keratinocytes and circulating in the serum of patients. This disease can be reproduced in neonatal mice by passive transfer of patients' IgG, indicating that humoral immunity plays an important role in the pathogenesis of PV. Currently, the role of T lymphocytes in the development of PV is not clear. Here, we report that three immunoreactive segments of the ectodomain of Dsg3 specifically induced proliferation of T cells from PV patients. We found that T lymphocytes from 13 out of 14 patients responded to at least one of three Dsg3 peptides. T cells from controls and other patient groups did not respond to these Dsg3 peptides. The major T cell population stimulated by these Dsg3 peptides was CD4 positive. Dsg3-specific T cell lines and clones were developed and were shown to express a CD4 positive memory T cell phenotype. Upon stimulation, these cell lines and clones secreted a Th2-like cytokine profile. The Dsg3 responses of these T cells were restricted to HLA-DR, and not -DQ and -DP, of the major histocompatibility complex. This information will help to elucidate the cellular immune abnormalities leading to production of pathogenic IgG autoantibodies in patients with PV.

AB - Pemphigus vulgaris (PV) is a cutaneous autoimmune disease characterized by blister formation in the suprabasilar layers of skin and mucosae and anti- desmoglein-3 (Dsg3) autoantibodies bound to the surface of lesional keratinocytes and circulating in the serum of patients. This disease can be reproduced in neonatal mice by passive transfer of patients' IgG, indicating that humoral immunity plays an important role in the pathogenesis of PV. Currently, the role of T lymphocytes in the development of PV is not clear. Here, we report that three immunoreactive segments of the ectodomain of Dsg3 specifically induced proliferation of T cells from PV patients. We found that T lymphocytes from 13 out of 14 patients responded to at least one of three Dsg3 peptides. T cells from controls and other patient groups did not respond to these Dsg3 peptides. The major T cell population stimulated by these Dsg3 peptides was CD4 positive. Dsg3-specific T cell lines and clones were developed and were shown to express a CD4 positive memory T cell phenotype. Upon stimulation, these cell lines and clones secreted a Th2-like cytokine profile. The Dsg3 responses of these T cells were restricted to HLA-DR, and not -DQ and -DP, of the major histocompatibility complex. This information will help to elucidate the cellular immune abnormalities leading to production of pathogenic IgG autoantibodies in patients with PV.

KW - cytokines

KW - desmoglein-3

KW - MHC II restriction

KW - pemphigus vulgaris

KW - T lymphocytes

UR - http://www.scopus.com/inward/record.url?scp=0031028992&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031028992&partnerID=8YFLogxK

M3 - Article

C2 - 9011573

AN - SCOPUS:0031028992

VL - 99

SP - 31

EP - 40

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 1

ER -