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

A total of 27 T-lymphocyte cell strains were 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-gamma 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-gamma 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.