Intralesional t-lymphocyte activation as a mediator of psoriatic epidermal hyperplasia

Z. Bata-Csorgo, C. Hammerberg, J. J. Voorhees, K. D. Cooper

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

An early cellular event in the development of psoriatic lesions is infiltration of target tissue by macrophages and activated T lymphocytes. Lesional psoriatic skin contains activated memory T lymphocytes with production of mRNA for lymphokines such as interleukin-2, interferon-γ, and tumor necrosis factor-α that is elevated relative to normal or uninvolved psoriatic skin. That the T-cell activation and cellular lymphokine production have a crucial role in the maintenance of epidermal hyperplasia in the psoriatic lesion is indicated by the beneficial effect of immunosuppressive agents in the treatment of psoriasis (cyclosporin A, FK506, anti-CD3, anti-CD4). A link between immune activation and psoriasis is also indicated by immunogenetic associations in this disease. Also, psoriatic keratinocytes appear to have been modulated by T-cell lymphokines in vivo, because they abnormally express molecules uniquely induced on keratinocytcs by the T-cell product interferon-γ. Indeed, T cells producing interferon-γ have been cloned from psoriatic lesions, and they are able to induce keratinocyte class II major histocompatibility complex and intercellular adhesion molecule expression. These lesion-derived T-cell clones can induce growth of keratinocytes, and specifically lesional psoriatic T cells produce factors that induce increased keratinocyte colony formation, as we}l as increased cell cycle entry of the normally quiescent stem cell population. Interferon-γ, although a growth inhibitor on its own, acts cooperatively with other T-cell-produced growth factors to cause keratinocyte growth induction. Furthermore, relative to normal stem cells, keratinocyte stem cells (β1 integrin+ K1/K10-) in psoriatic uninvolved epidermis are significantly hyperresponsive to the growth-stimulatory lymphokine milieu created by lesional T lymphocytes. Whether such abnormalities in responsiveness are associated with new genetic linkages reported in families of psoriasis patients is unknown. As the epidermis of lesional psoriatic skin can be demonstrated to produce elevated Ievels of factors that can further potentiate T-cell activation, a self-sustaining cycle can be constructed of T-cell recruitment, intralesional activation, release of factors that preferentially stimulate psoriatic epidermal stem cells to proliferate, and further epidermal potentiation of the T-cell-mediated lesions.

Original languageEnglish
Pages (from-to)S89-S94
JournalJournal of Investigative Dermatology
Volume105
Issue number1 SUPPL.
DOIs
Publication statusPublished - Jan 1 1995

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Fingerprint Dive into the research topics of 'Intralesional t-lymphocyte activation as a mediator of psoriatic epidermal hyperplasia'. Together they form a unique fingerprint.

  • Cite this