Skin-infiltrating lymphocytes in normal and disordered skin: activation signals and functional roles in psoriasis and mycosis fungoides-type cutaneous T cell lymphoma.

Abstract

T lymphocytes recruited into the skin can experience several different outcomes. On the one hand, they may be recruited by adhesion molecules and chemoattractants to enter the perivascular space, but never undergo activation. Other T cells undergo activation and further differentiation under the influence of the cutaneous milieu. These activated lymphocytes then coordinate specific and non-specific immune responses characteristic of inflamed tissue. We have explored two models for studying the activation and function of skin infiltrating T lymphocytes (SIL's). In the first model, we have identified a family of Langerhans cell-related professional dendritic antigen presenting cells that exist in the epidermis and dermis of normal skin, atopic skin, and mycosis fungoides skin. These have APC abilities to activate freshly recruited resting blood T cells that are distinct from another family of macrophage-related cells abnormally present in sunburned or psoriatic skin. In the second model, we examined the function of cells that have already been recruited into the skin of patients with psoriasis and mycosis fungoides. Lesional psoriasis and mycosis fungoides T cells exhibited a variety of T cell receptor gene rearrangements, conclusively demonstrating that heterogeneous populations of T lymphocytes exist in inflamed human skin. From psoriasis, clones were identified that were particularly effective at inducing normal keratinocytes to assume "psoriatic" phenotypic features and functions. Thus, lesional psoriatic SIL's could induce HLA-DR, ICAM, and CDw60 on normal keratinocytes. In addition, psoriatic SIL's induced increased keratinocyte proliferation and cytokine profile changes characteristic of psoriatic epidermis.(ABSTRACT TRUNCATED AT 250 WORDS)