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-gamma, and tumor necrosis factor-alpha 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 og
keratinocytes by the T-cell product interferon-gamma. Indeed, T cells producing interferon-gamma
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 well as increased cell cycle entry of the normally quiescent stem cell
population, Interferon-gamma, 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 (beta 1 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 levels 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.
