CD4⁺ T cells from MF skin lesions have an effector memory phenotype, but T cells from L-CTCL skin lesions have central memory characteristics. (A) Normal skin and the skin lesions of patients with L-CTCL contained a clear population of L-selectin and CCR7 coexpressing central memory T cells. However, T cells isolated from the skin lesions of stable patch plaque MF lacked coexpression of the central memory markers CCR7/L-selectin but did express the skin homing addressins CCR4 and CLA. All histograms are gated to show only CD4⁺ T cells. CCR4 was expressed by virtually all T cells, whereas CLA expression was frequent but not universal. Similar to results in L-CTCL patients, expression of CD45RO and CD45RA varied among patients. Four representative patients are shown; similar results were obtained in a total of 15 patients. (B) Clonal malignant T cells in the skin lesions of patients with L-CTCL expressed both L-selectin/CCR7 and skin homing addressins. Malignant T cells from the skin lesions of patients with L-CTCL were selectively studied by gating on T cells expressing the malignant Vβ subfamily (black cells, Vβ1 for patient 333 and Vβ13.1 for patient 330). Histograms are gated to show only malignant T cells. Malignant clonal T cells showed near-universal expression of the central memory markers L-selectin and CCR7 as well as high expression of the skin homing addressins CLA and CCR4. Results from 2 patients are shown; similar findings were observed in T cells isolated from the skin lesions of 4 additional L-CTCL patients. (C) In contrast, clonal T cells arising in MF skin lesions lacked central memory markers. Clonal malignant T cells expressing TCR-Vβ13.1 were evident in the skin lesions of a patient with MF (black cells represent remaining histograms gated to display only clonal malignant cells). Clonal malignant T cells lacked expression of the central memory markers L-selectin/CCR7 but expressed CCR4, and the majority coexpressed CLA. (D) Microarray gene expression analysis demonstrated that T cells from MF skin lesions expressed low levels of CD27 compared with clonal malignant T cells isolated from the blood of L-CTCL patients. The mean ± SEM of 5 MF patients, 3 normal skin patients, and 3 L-CTCL patients are shown. (E) Flow cytometric staining of T cells from the skin lesions of MF and L-CTCL confirmed that CD4⁺ T cells in MF show loss of CD27, consistent with an effector memory phenotype. T cells from the skin lesion of a representative patient with L-CTCL expressed CD27.