title: Cutaneous T-cell lymphoma lesional epidermal cells activate autologous CD4+ T lymphocytes: involvement of both CD1+OKM5+ and CD1+OKM5- antigen-presenting cells.
abstract: Cutaneous T-cell lymphoma is characterized by infiltration of the skin by activated CD4+ T lymphocytes. The mechanism by which these T lymphocytes achieve and maintain their activated state is unknown. Antigen-specific activation of T lymphocytes is dependent upon antigen-presenting cells which express HLA-DR class II major histocompatibility complex molecules, such as epidermal Langerhans cells. In addition to CD1+DR+ Langerhans cells, cutaneous T-cell lymphoma lesional epidermis contains major histocompatibility complex class II positive non-Langerhans cell populations, including CD1+OKM5+ bone-marrow-derived cells and DR+ keratinocytes. We asked whether any of these epidermal cell populations demonstrate capacity to activate T lymphocytes. Various numbers of epidermal cells from uninvolved and involved cutaneous T-cell lymphoma plaques were therefore used to stimulate autologous CD4+ and CD8+ T lymphocytes in the absence of exogenous antigen. Involved epidermal cells potently induced proliferation of CD4+ T lymphocytes (S.I. +/- SEM = 466 +/- 45). In contrast, uninvolved epidermal cells only induced background levels of proliferation (S.I. +/- SEM = 2 +/- 0.5, N = 8, p less than 0.01). Neither involved nor uninvolved epidermal cells were able directly to activate CD8+ lymphocytes. The capability of involved epidermal cells to activate CD4+ T lymphocytes was dependent upon CD1+DR+ leukocytes and not DR+ keratinocytes, because depletion of either HLA-DR+, CD1+ or HLe1+ epidermal cells totally abrogated the T-lymphocyte proliferation. Interestingly, on a cell per cell basis CD1+DR+ cells obtained from involved skin, demonstrated relative to CD1+DR+ cells from uninvolved skin, enhanced capacity to activate CD4+ T lymphocytes. Furthermore, CD1+OKM5+ cells from involved epidermis stimulated autologous CD4+ T lymphocytes. This indicates that a unique hitherto undescribed CD1+OKM5+ epidermal antigen-presenting cell population may participate in T-lymphocyte activation. These findings provide support for the concept that the epidermal cells in cutaneous T-cell lymphoma patients, particularly the antigen-presenting cells, may contribute significantly to the activation of CD4+ malignant and/or non-malignant inflammatory T lymphocytes within the skin.
authors.affiliation: Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark.
authors.forename: E R
authors.initials: ER
authors.lastname: Hansen
authors.forename: O
authors.initials: O
authors.lastname: Baadsgaard
authors.forename: S
authors.initials: S
authors.lastname: Lisby
authors.forename: K D
authors.initials: KD
authors.lastname: Cooper
authors.forename: K
authors.initials: K
authors.lastname: Thomsen
authors.forename: G L
authors.initials: GL
authors.lastname: Vejlsgaard
mesh_terms: D000938:Antigen-Presenting Cells; D015703:Antigens, CD / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D015603:Keratinocytes / Q000276:immunology; D008213:Lymphocyte Activation; D008223:Lymphoma / Q000276:immunology*; D012878:Skin Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D015703:Antigens, CD; D006684:HLA-DR Antigens