Malignant T cells from the blood of patients with L-CTCL have a central memory T-cell phenotype. (A) Flow cytometric analysis of clonal malignant T cells isolated from the blood of an L-CTCL patient with a TCR-Vβ17 malignant clone demonstrated that malignant T cells expressed high levels of the central memory T-cell markers L-selectin and CCR7. CCR4 was also expressed at high levels, but expression of other skin homing addressins (CLA, CCR6, and CCR10) was variable. There was no detectable expression of the gut homing addressins α₄β₇-integrin and CCR9. (B) CCR4 and CCR7 expressed by malignant T cells in L-CTCL were functional as demonstrated by their ability to support migration to the CCR4 ligand CCL22 and the CCR7 ligand CCL21 in in vitro T-cell migration assays. Shown are the mean ± SD migration of clonal malignant T cells from 3 L-CTCL donors (left panel) and the naive (center panel) and CLA⁺ memory T cells (right panel) from 3 normal donors. As expected, normal naive T cells responded only to CCR7 ligand. (C) Clonal malignant T cells from L-CTCL patients expressed high levels of CD27, consistent with a central memory T-cell phenotype, but expression of CD45RA varied among patients. CD4⁺ CD3⁺ T cells from a normal donor are shown on the left. The CD27-negative effector T-cell population observed in normal donors is indicated by an arrow. The right 3 panels show 3 L-CTCL patients, and histograms are gated to show only the CD4⁺ clonal malignant T-cell populations. CD27 was uniformly expressed on malignant cells from all donors, but the expression of CD45RA was variable. (D) Analysis of 11 additional L-CTCL patients with identifiable malignant clones produced similar results. Shown are the mean ± SD of surface marker expression of the CD3⁺/CD4⁺ cells expressing the expanded TCR-Vβ clonotype.