Sézary cells exhibit a wide range of different Th and maturation phenotypes illustrative of inter- and intrapatient heterogeneity. (A) Reference data set of phenotypically defined classical and nonclassical Th subsets depicted in an APS plot based on the expression patterns of CD183, CD194, CD196, and CCR10 on (left) normal CD4⁺ T cells derived from 10 age- and sex-matched HCs with corresponding Th population medians (larger dots) and second standard deviation lines. To compare, 3 examples of samples from patients with SS, with Sézary cells (red) displaying phenotypes matching (from left to right) predominantly 1 (SS case 4; that of Th2 [77% of tumor cells]), 2 (SS case 1; CD194⁺CCR10⁺ [77%] and Th22 [20%]), or multiple (SS case 13; Th2 [60%], Th17 [21%], and Th22 [7%]) Th subsets at one single time-point measurement. (Right) Merged file of 24 SS initial samples exhibiting the aberrant and heterogeneous expression patterns of Sézary cells compared with the normal reference data set. Given are classical Th1 (CD183⁺), Th2 (CD194⁺), Th17 (CD194⁺CD196⁺), Th22 (CD194⁺CD196⁺CCR10⁺), Th1/Th17 (CD183⁺CD196⁺), and most common nonclassical CD194⁺CCR10⁺, CD183⁺CD194⁺, CD183⁺CD194⁺CD196⁺, CD183⁺CD194⁺CCR10⁺, and nonnaïve ⁻CD183⁻CD194⁻CD196⁻CCR10⁻ Th subsets. (B) An APS plot comparing the 5 main maturation stages of normally distributed CD4⁺ T-cell populations (2.0 standard deviation curve is shown) derived from 10 age- and sex-matched HCs with their corresponding medians (larger dots) for each maturation stage (left). Maturation stages were based on characteristic CD27, CD45RA, and CD62L expression patterns. Examples of 3 samples from patients with SS showing aberrant CD4⁺ T cells (small red dots) that exhibit predominantly (from left to right) (SS case 22) CM, (SS case 21) CM and TM, or (SS case 15) CM, TM, and PM phenotypes. (Right) All phenotypically aberrant CD4⁺ T cells from 24 samples from patients with SS merged into 1 file with their corresponding population medians (larger dots) of each patient sample. CM, central memory; N, naïve-like; PM, peripheral memory; TM, transitional memory.