Skin-homing CD8+ T lymphocytes Show Preferential Growth in vitro and Suppress CD4+ T-cell Proliferation in Patients with Early Stages of Cutaneous T-cell Lymphoma
Kristian Thestrup-Pedersen, Ranjit Parhar, Kaida Wu, Per-Anders Bertilsson, Brian Meyer, Sayeda Abu-Amero, Bo Hainau, Abdullah AlEisa, Abdullah AlFadley, Issam Hamadah, Abdulmajeed AlAjlan, Khalid Al-Hussein, Futwan Al-Mohanna
DOI: 10.2340/00015555-0206
Abstract
A total of 27 T-lymphocyte cell strains wereb established from skin biopsies of 24 patients with various stages of cutaneous T-cell lymphoma (CTCL) by addition of the T-cell growth factors interleukin (IL)-2 and IL-4. Cellular proliferation and phenotypic changes were measured over 3 months in culture, and T-cell clones were studied using T-cell receptor-γ re-arrangement techniques. An average outgrowth of 134 million T lymphocytes from a 4-mm skin biopsy was observed over 2 months. Initially, most T cells expressed the CD4+ phenotype. In 17 cell strains from patients with early CTCL a statistically significant predominance of CD8+ T-lymphocytes developed over 8-weeks' culture, indicating that CD8+ T cells controlled the growth of CD4+ T cells, whereas CD4+ T cells were predominant in cell strains from advanced CTCL (p<0.05). TCR-γ re-arrangement studies revealed, on average, 12 T-cell clones per cell strain, which was reduced over time to 6 T-cell clones per cell strain. Lymphocytes from peripheral blood could kill lymphocytes from an autologous cell strain, suggesting the presence of autoreactive cytotoxic T cells. Our study suggests how skin-homing CD8+ T lymphocytes from patients with early stage CTCL can suppress the in vitro growth of skin-homing CD4+ T-lymphocytes, indicating immune surveillance.
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