Characterization of a T cell line bearing natural killer receptors and capable of creating psoriasis in a SCID mouse model system

Brian J. Nickoloff, Brian Bonish, Barbara Bei Huang, Steven A. Porcelli

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

T cells bearing natural killer receptors (NKRs) such as CD94 and CD161 are present in psoriasis. These immunocytes express several receptors for both classical and non-classical class I MHC molecules. Whether T cells bearing NKRs in psoriatic lesions represent immunoregulatory versus pathogenic immunocytes or are just bystander cells is unclear. To address this issue, a CD94+/CD161+ T cell line was established from a psoriatic patient using IL-2/superantigens, and the interaction between NK-T cells and keratinocytes was characterized using in-vitro and in-vivo assays. Upon incubation between NK-T cells and CD1d positive keratinocytes, high levels of IFN-γ and IL-13 were produced. Cytokine production was inhibited by a mAb against CD1d, implicating recognition of this surface molecule in the T cell response. Furthermore when this line was injected into pre-psoriatic skin engrafted onto a SCID mouse, a psoriatic plaque was created. The hyperplastic epidermal keratinocytes diffusely expressed CD1d, and were infiltrated by CD161+ T cells. RNase protection assay revealed predominantly IFN-γ and IL-15 mRNAs, with barely detectable IL-13 mRNA in the acute lesion. These in-vivo findings demonstrated that this T cell line was pathogenic by creating a psoriatic plaque. The in-vitro results support a pathophysiologic role for interaction between T cells expressing NKRs and CD1d positive keratinocytes, with subsequent production of IFN-γ. Upon injection in-vivo, the cytokine network produced was characterized by an immunological response polarized towards Th1 rather than Th2 cytokines. Thus, this pathogenic cell line provides evidence that T cells bearing NKRs can directly provoke a Th1 disease such as psoriasis. (C) 2000 Elsevier Science Ireland Ltd.

Original languageEnglish (US)
Pages (from-to)212-225
Number of pages14
JournalJournal of Dermatological Science
Volume24
Issue number3
DOIs
StatePublished - 2000
Externally publishedYes

Fingerprint

Bearings (structural)
SCID Mice
T-cells
Psoriasis
T-Lymphocytes
Cell Line
Natural Killer Cell Receptors
Keratinocytes
Interleukin-13
Cytokines
Natural Killer Cells
Assays
Interleukin-15
Superantigens
Messenger RNA
Molecules
Ribonucleases
Interleukin-2
Skin

Keywords

  • Natural killer receptors
  • Psoriasis
  • SCID mouse model system
  • T cell

ASJC Scopus subject areas

  • Dermatology

Cite this

Characterization of a T cell line bearing natural killer receptors and capable of creating psoriasis in a SCID mouse model system. / Nickoloff, Brian J.; Bonish, Brian; Huang, Barbara Bei; Porcelli, Steven A.

In: Journal of Dermatological Science, Vol. 24, No. 3, 2000, p. 212-225.

Research output: Contribution to journalArticle

@article{d7d008a6e5ab4dbfa1a931e16e99ecae,
title = "Characterization of a T cell line bearing natural killer receptors and capable of creating psoriasis in a SCID mouse model system",
abstract = "T cells bearing natural killer receptors (NKRs) such as CD94 and CD161 are present in psoriasis. These immunocytes express several receptors for both classical and non-classical class I MHC molecules. Whether T cells bearing NKRs in psoriatic lesions represent immunoregulatory versus pathogenic immunocytes or are just bystander cells is unclear. To address this issue, a CD94+/CD161+ T cell line was established from a psoriatic patient using IL-2/superantigens, and the interaction between NK-T cells and keratinocytes was characterized using in-vitro and in-vivo assays. Upon incubation between NK-T cells and CD1d positive keratinocytes, high levels of IFN-γ and IL-13 were produced. Cytokine production was inhibited by a mAb against CD1d, implicating recognition of this surface molecule in the T cell response. Furthermore when this line was injected into pre-psoriatic skin engrafted onto a SCID mouse, a psoriatic plaque was created. The hyperplastic epidermal keratinocytes diffusely expressed CD1d, and were infiltrated by CD161+ T cells. RNase protection assay revealed predominantly IFN-γ and IL-15 mRNAs, with barely detectable IL-13 mRNA in the acute lesion. These in-vivo findings demonstrated that this T cell line was pathogenic by creating a psoriatic plaque. The in-vitro results support a pathophysiologic role for interaction between T cells expressing NKRs and CD1d positive keratinocytes, with subsequent production of IFN-γ. Upon injection in-vivo, the cytokine network produced was characterized by an immunological response polarized towards Th1 rather than Th2 cytokines. Thus, this pathogenic cell line provides evidence that T cells bearing NKRs can directly provoke a Th1 disease such as psoriasis. (C) 2000 Elsevier Science Ireland Ltd.",
keywords = "Natural killer receptors, Psoriasis, SCID mouse model system, T cell",
author = "Nickoloff, {Brian J.} and Brian Bonish and Huang, {Barbara Bei} and Porcelli, {Steven A.}",
year = "2000",
doi = "10.1016/S0923-1811(00)00120-1",
language = "English (US)",
volume = "24",
pages = "212--225",
journal = "Journal of Dermatological Science",
issn = "0923-1811",
publisher = "Elsevier Ireland Ltd",
number = "3",

}

TY - JOUR

T1 - Characterization of a T cell line bearing natural killer receptors and capable of creating psoriasis in a SCID mouse model system

AU - Nickoloff, Brian J.

AU - Bonish, Brian

AU - Huang, Barbara Bei

AU - Porcelli, Steven A.

PY - 2000

Y1 - 2000

N2 - T cells bearing natural killer receptors (NKRs) such as CD94 and CD161 are present in psoriasis. These immunocytes express several receptors for both classical and non-classical class I MHC molecules. Whether T cells bearing NKRs in psoriatic lesions represent immunoregulatory versus pathogenic immunocytes or are just bystander cells is unclear. To address this issue, a CD94+/CD161+ T cell line was established from a psoriatic patient using IL-2/superantigens, and the interaction between NK-T cells and keratinocytes was characterized using in-vitro and in-vivo assays. Upon incubation between NK-T cells and CD1d positive keratinocytes, high levels of IFN-γ and IL-13 were produced. Cytokine production was inhibited by a mAb against CD1d, implicating recognition of this surface molecule in the T cell response. Furthermore when this line was injected into pre-psoriatic skin engrafted onto a SCID mouse, a psoriatic plaque was created. The hyperplastic epidermal keratinocytes diffusely expressed CD1d, and were infiltrated by CD161+ T cells. RNase protection assay revealed predominantly IFN-γ and IL-15 mRNAs, with barely detectable IL-13 mRNA in the acute lesion. These in-vivo findings demonstrated that this T cell line was pathogenic by creating a psoriatic plaque. The in-vitro results support a pathophysiologic role for interaction between T cells expressing NKRs and CD1d positive keratinocytes, with subsequent production of IFN-γ. Upon injection in-vivo, the cytokine network produced was characterized by an immunological response polarized towards Th1 rather than Th2 cytokines. Thus, this pathogenic cell line provides evidence that T cells bearing NKRs can directly provoke a Th1 disease such as psoriasis. (C) 2000 Elsevier Science Ireland Ltd.

AB - T cells bearing natural killer receptors (NKRs) such as CD94 and CD161 are present in psoriasis. These immunocytes express several receptors for both classical and non-classical class I MHC molecules. Whether T cells bearing NKRs in psoriatic lesions represent immunoregulatory versus pathogenic immunocytes or are just bystander cells is unclear. To address this issue, a CD94+/CD161+ T cell line was established from a psoriatic patient using IL-2/superantigens, and the interaction between NK-T cells and keratinocytes was characterized using in-vitro and in-vivo assays. Upon incubation between NK-T cells and CD1d positive keratinocytes, high levels of IFN-γ and IL-13 were produced. Cytokine production was inhibited by a mAb against CD1d, implicating recognition of this surface molecule in the T cell response. Furthermore when this line was injected into pre-psoriatic skin engrafted onto a SCID mouse, a psoriatic plaque was created. The hyperplastic epidermal keratinocytes diffusely expressed CD1d, and were infiltrated by CD161+ T cells. RNase protection assay revealed predominantly IFN-γ and IL-15 mRNAs, with barely detectable IL-13 mRNA in the acute lesion. These in-vivo findings demonstrated that this T cell line was pathogenic by creating a psoriatic plaque. The in-vitro results support a pathophysiologic role for interaction between T cells expressing NKRs and CD1d positive keratinocytes, with subsequent production of IFN-γ. Upon injection in-vivo, the cytokine network produced was characterized by an immunological response polarized towards Th1 rather than Th2 cytokines. Thus, this pathogenic cell line provides evidence that T cells bearing NKRs can directly provoke a Th1 disease such as psoriasis. (C) 2000 Elsevier Science Ireland Ltd.

KW - Natural killer receptors

KW - Psoriasis

KW - SCID mouse model system

KW - T cell

UR - http://www.scopus.com/inward/record.url?scp=0033748019&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033748019&partnerID=8YFLogxK

U2 - 10.1016/S0923-1811(00)00120-1

DO - 10.1016/S0923-1811(00)00120-1

M3 - Article

C2 - 11084303

AN - SCOPUS:0033748019

VL - 24

SP - 212

EP - 225

JO - Journal of Dermatological Science

JF - Journal of Dermatological Science

SN - 0923-1811

IS - 3

ER -