Differential effects of cyclosporine A on Langerhans cells and regulatory T-cell populations in severe psoriasis

an immunohistochemical and flow cytometric analysis

C Horrocks, J I Duncan, H F Sewell, Anthony Ormerod, A W Thomson

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Systemic administration of cyclosporine A (Cy-A; initial dose 5 or 2.5 mg/kg/day) to patients with severe chronic plaque psoriasis produced marked reductions in psoriasis area and severity index within 4 weeks. The clinical response was accompanied, within 1 week, by progressive reductions in T-cell subpopulations (CD3+ and CD4+) and in numbers of interleukin-2 receptor (IL-2-R)-positive (CD25+) cells within lesional skin. Over the first 4 weeks of treatment, these changes were accompanied by reductions in DR+ cells within the epidermis (minor) and dermis (substantial). In contrast, numbers of epidermal CD1+ cells increased substantially during resolution of the skin lesions. Unlike lesional skin, however, no significant changes in absolute numbers of circulating immunoregulatory T-cell populations, including helper/inducer (CD45R) and suppressor/inducer (CD29W) subsets, quantified by dual immunofluorescence labelling, were detected. Moreover, numbers of blood-borne HLA-DR, IL-2-R and transferrin receptor (CD71) positive lymphocytes were unaffected by Cy-A therapy, nor were any differences detected between psoriatic patients and normal controls using these cell markers. Our data suggest that the immunoregulatory effects of Cy-A in psoriasis are mediated via lesional T lymphocytes and that epidermal CD1+ DR- dendritic cells may play an influential role in the regulation of T-cell function and keratinocyte growth during resolution of the skin lesions.
Original languageEnglish
Pages (from-to)559-570
Number of pages12
JournalJournal of Autoimmunity
Volume3
Issue number5
DOIs
Publication statusPublished - 1 Oct 1990

Fingerprint

Langerhans Cells
Regulatory T-Lymphocytes
Psoriasis
Cyclosporine
T-Lymphocytes
Skin
Interleukin-2 Receptors
Population
Transferrin Receptors
HLA-DR Antigens
Dermis
Keratinocytes
Epidermis
Dendritic Cells
Fluorescent Antibody Technique
Lymphocytes
Therapeutics
Growth

Keywords

  • Adult
  • Aged
  • Antibodies, Monoclonal
  • Antigens, Differentiation
  • Autoimmune Diseases
  • Cyclosporins
  • Female
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Immunophenotyping
  • Langerhans Cells
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Psoriasis
  • Skin
  • T-Lymphocyte Subsets
  • T-Lymphocytes

Cite this

Differential effects of cyclosporine A on Langerhans cells and regulatory T-cell populations in severe psoriasis : an immunohistochemical and flow cytometric analysis. / Horrocks, C; Duncan, J I; Sewell, H F; Ormerod, Anthony; Thomson, A W.

In: Journal of Autoimmunity, Vol. 3, No. 5, 01.10.1990, p. 559-570.

Research output: Contribution to journalArticle

@article{c43732766867452e9102a8a3c0ff02f1,
title = "Differential effects of cyclosporine A on Langerhans cells and regulatory T-cell populations in severe psoriasis: an immunohistochemical and flow cytometric analysis",
abstract = "Systemic administration of cyclosporine A (Cy-A; initial dose 5 or 2.5 mg/kg/day) to patients with severe chronic plaque psoriasis produced marked reductions in psoriasis area and severity index within 4 weeks. The clinical response was accompanied, within 1 week, by progressive reductions in T-cell subpopulations (CD3+ and CD4+) and in numbers of interleukin-2 receptor (IL-2-R)-positive (CD25+) cells within lesional skin. Over the first 4 weeks of treatment, these changes were accompanied by reductions in DR+ cells within the epidermis (minor) and dermis (substantial). In contrast, numbers of epidermal CD1+ cells increased substantially during resolution of the skin lesions. Unlike lesional skin, however, no significant changes in absolute numbers of circulating immunoregulatory T-cell populations, including helper/inducer (CD45R) and suppressor/inducer (CD29W) subsets, quantified by dual immunofluorescence labelling, were detected. Moreover, numbers of blood-borne HLA-DR, IL-2-R and transferrin receptor (CD71) positive lymphocytes were unaffected by Cy-A therapy, nor were any differences detected between psoriatic patients and normal controls using these cell markers. Our data suggest that the immunoregulatory effects of Cy-A in psoriasis are mediated via lesional T lymphocytes and that epidermal CD1+ DR- dendritic cells may play an influential role in the regulation of T-cell function and keratinocyte growth during resolution of the skin lesions.",
keywords = "Adult, Aged, Antibodies, Monoclonal, Antigens, Differentiation, Autoimmune Diseases, Cyclosporins, Female, Flow Cytometry, Humans, Immunohistochemistry, Immunophenotyping, Langerhans Cells, Lymphocyte Activation, Male, Middle Aged, Psoriasis, Skin, T-Lymphocyte Subsets, T-Lymphocytes",
author = "C Horrocks and Duncan, {J I} and Sewell, {H F} and Anthony Ormerod and Thomson, {A W}",
year = "1990",
month = "10",
day = "1",
doi = "10.1016/S0896-8411(05)80021-6",
language = "English",
volume = "3",
pages = "559--570",
journal = "Journal of Autoimmunity",
issn = "0896-8411",
publisher = "Academic Press Inc.",
number = "5",

}

TY - JOUR

T1 - Differential effects of cyclosporine A on Langerhans cells and regulatory T-cell populations in severe psoriasis

T2 - an immunohistochemical and flow cytometric analysis

AU - Horrocks, C

AU - Duncan, J I

AU - Sewell, H F

AU - Ormerod, Anthony

AU - Thomson, A W

PY - 1990/10/1

Y1 - 1990/10/1

N2 - Systemic administration of cyclosporine A (Cy-A; initial dose 5 or 2.5 mg/kg/day) to patients with severe chronic plaque psoriasis produced marked reductions in psoriasis area and severity index within 4 weeks. The clinical response was accompanied, within 1 week, by progressive reductions in T-cell subpopulations (CD3+ and CD4+) and in numbers of interleukin-2 receptor (IL-2-R)-positive (CD25+) cells within lesional skin. Over the first 4 weeks of treatment, these changes were accompanied by reductions in DR+ cells within the epidermis (minor) and dermis (substantial). In contrast, numbers of epidermal CD1+ cells increased substantially during resolution of the skin lesions. Unlike lesional skin, however, no significant changes in absolute numbers of circulating immunoregulatory T-cell populations, including helper/inducer (CD45R) and suppressor/inducer (CD29W) subsets, quantified by dual immunofluorescence labelling, were detected. Moreover, numbers of blood-borne HLA-DR, IL-2-R and transferrin receptor (CD71) positive lymphocytes were unaffected by Cy-A therapy, nor were any differences detected between psoriatic patients and normal controls using these cell markers. Our data suggest that the immunoregulatory effects of Cy-A in psoriasis are mediated via lesional T lymphocytes and that epidermal CD1+ DR- dendritic cells may play an influential role in the regulation of T-cell function and keratinocyte growth during resolution of the skin lesions.

AB - Systemic administration of cyclosporine A (Cy-A; initial dose 5 or 2.5 mg/kg/day) to patients with severe chronic plaque psoriasis produced marked reductions in psoriasis area and severity index within 4 weeks. The clinical response was accompanied, within 1 week, by progressive reductions in T-cell subpopulations (CD3+ and CD4+) and in numbers of interleukin-2 receptor (IL-2-R)-positive (CD25+) cells within lesional skin. Over the first 4 weeks of treatment, these changes were accompanied by reductions in DR+ cells within the epidermis (minor) and dermis (substantial). In contrast, numbers of epidermal CD1+ cells increased substantially during resolution of the skin lesions. Unlike lesional skin, however, no significant changes in absolute numbers of circulating immunoregulatory T-cell populations, including helper/inducer (CD45R) and suppressor/inducer (CD29W) subsets, quantified by dual immunofluorescence labelling, were detected. Moreover, numbers of blood-borne HLA-DR, IL-2-R and transferrin receptor (CD71) positive lymphocytes were unaffected by Cy-A therapy, nor were any differences detected between psoriatic patients and normal controls using these cell markers. Our data suggest that the immunoregulatory effects of Cy-A in psoriasis are mediated via lesional T lymphocytes and that epidermal CD1+ DR- dendritic cells may play an influential role in the regulation of T-cell function and keratinocyte growth during resolution of the skin lesions.

KW - Adult

KW - Aged

KW - Antibodies, Monoclonal

KW - Antigens, Differentiation

KW - Autoimmune Diseases

KW - Cyclosporins

KW - Female

KW - Flow Cytometry

KW - Humans

KW - Immunohistochemistry

KW - Immunophenotyping

KW - Langerhans Cells

KW - Lymphocyte Activation

KW - Male

KW - Middle Aged

KW - Psoriasis

KW - Skin

KW - T-Lymphocyte Subsets

KW - T-Lymphocytes

U2 - 10.1016/S0896-8411(05)80021-6

DO - 10.1016/S0896-8411(05)80021-6

M3 - Article

VL - 3

SP - 559

EP - 570

JO - Journal of Autoimmunity

JF - Journal of Autoimmunity

SN - 0896-8411

IS - 5

ER -