Identification and quantitation of interferon-γ producing T cells in psoriatic lesions

Localization to both CD4+ and CD8+ subsets

Sarolta K. Szabo, Craig Hammerberg, Yuichi Yoshida, Z. Bata-Csörgő, Kevin D. Cooper

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

Interferon-γ (IFN-γ) produced by lesional T cell clones is critical for the induction into G1 of the cell cycle by psoriatic keratinocyte stem cells; however, direct data demonstrating psoriatic lesional T cell subset IFN-γ expression, and quantitation at a single cell level to calculate in vivo proportions, are lacking. In this study, using flow cytometry of freshly isolated normal and psoriatic lesional T cells from keratome biopsies, we found elevated CD3+, CD4+, and CD8+ T cells in all compartments of psoriatic skin, compared with normals. Using Brefeldin A to induce short- term intracellular accumulation of IFN-γ in T cells capable of IFN-γ production, we found that 90% of psoriatic patients have IFN-γ-producing T cells at a greater proportion of their CD3+ cells than normals, with a mean of 16% ± 3%, as compared with 4% ± 2% in normal epidermis (p = 0.01). Expressed as density in the tissue, the IFN-γ+ CD3+ cell number in psoriatic epidermis was 97 ± 22 per mm2 surface area, as compared with 4.4 ± 1.8 per mm2 of normal epidermis (p = 0.002). Thus, the total number of IFN-γ+ CD3+ T cells in the skin of a patient with 20% involvement is estimated to be 3.9 x 108. CD4+ and CD8+ IFN-γ+ T cells were both elevated in psoriatic epidermis (p = 0.04 and p = 0.008, respectively) relative to normal skin. In the dermis, only 44% of patients demonstrated a higher percentage of IFN-γ-producing T cells than did normals (p = 0.1), possibly indicating dilution, in some patients, by fresh infiltrating T cells. Interleukin-4 was not found by a combination of flow cytometry, reverse transcriptase-polymerase chain reaction, western blot, and immunoprecipitation. In conclusion, a significant portion of lesional T cells in psoriasis are IFN-γ producing, without interleukin-4. The increased numbers of both IFN-γ+ CD4+ and IFN-γ+ CD8 + T cells indicate that both CD4+ and CD8+ IFN-γ+ T cells are present in appropriate anatomic locations to sustain the lesional pathology.

Original languageEnglish
Pages (from-to)1072-1078
Number of pages7
JournalJournal of Investigative Dermatology
Volume111
Issue number6
DOIs
Publication statusPublished - 1998

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T-cells
Interferons
T-Lymphocytes
Epidermis
Skin
Flow cytometry
Interleukin-4
Flow Cytometry
Brefeldin A
Biopsy
Polymerase chain reaction
RNA-Directed DNA Polymerase
T-Lymphocyte Subsets
Pathology
Dermis
Stem cells
Reverse Transcriptase Polymerase Chain Reaction
Keratinocytes
Psoriasis
Immunoprecipitation

Keywords

  • IFN-γ/psoriasis
  • T cells

ASJC Scopus subject areas

  • Dermatology

Cite this

Identification and quantitation of interferon-γ producing T cells in psoriatic lesions : Localization to both CD4+ and CD8+ subsets. / Szabo, Sarolta K.; Hammerberg, Craig; Yoshida, Yuichi; Bata-Csörgő, Z.; Cooper, Kevin D.

In: Journal of Investigative Dermatology, Vol. 111, No. 6, 1998, p. 1072-1078.

Research output: Contribution to journalArticle

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abstract = "Interferon-γ (IFN-γ) produced by lesional T cell clones is critical for the induction into G1 of the cell cycle by psoriatic keratinocyte stem cells; however, direct data demonstrating psoriatic lesional T cell subset IFN-γ expression, and quantitation at a single cell level to calculate in vivo proportions, are lacking. In this study, using flow cytometry of freshly isolated normal and psoriatic lesional T cells from keratome biopsies, we found elevated CD3+, CD4+, and CD8+ T cells in all compartments of psoriatic skin, compared with normals. Using Brefeldin A to induce short- term intracellular accumulation of IFN-γ in T cells capable of IFN-γ production, we found that 90{\%} of psoriatic patients have IFN-γ-producing T cells at a greater proportion of their CD3+ cells than normals, with a mean of 16{\%} ± 3{\%}, as compared with 4{\%} ± 2{\%} in normal epidermis (p = 0.01). Expressed as density in the tissue, the IFN-γ+ CD3+ cell number in psoriatic epidermis was 97 ± 22 per mm2 surface area, as compared with 4.4 ± 1.8 per mm2 of normal epidermis (p = 0.002). Thus, the total number of IFN-γ+ CD3+ T cells in the skin of a patient with 20{\%} involvement is estimated to be 3.9 x 108. CD4+ and CD8+ IFN-γ+ T cells were both elevated in psoriatic epidermis (p = 0.04 and p = 0.008, respectively) relative to normal skin. In the dermis, only 44{\%} of patients demonstrated a higher percentage of IFN-γ-producing T cells than did normals (p = 0.1), possibly indicating dilution, in some patients, by fresh infiltrating T cells. Interleukin-4 was not found by a combination of flow cytometry, reverse transcriptase-polymerase chain reaction, western blot, and immunoprecipitation. In conclusion, a significant portion of lesional T cells in psoriasis are IFN-γ producing, without interleukin-4. The increased numbers of both IFN-γ+ CD4+ and IFN-γ+ CD8 + T cells indicate that both CD4+ and CD8+ IFN-γ+ T cells are present in appropriate anatomic locations to sustain the lesional pathology.",
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AU - Bata-Csörgő, Z.

AU - Cooper, Kevin D.

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