Circulating CD4 + T-Cell differentiation subsets show a distinct distribution in HTLV-1–associated adult T-Cell leukemia/lymphoma

Human T-cell lymphotropic virus type 1 (HTLV-1) establishes lifelong infection in CD4 + T lymphocytes and can cause adult T-cell leukemia/lymphoma (ATLL). The distribution of circulating CD4 + T-cell differentiation subsets across asymptomatic infection and ATLL, and its relationship with presumed transmission route, remain incompletely characterized. This single-center, cross-sectional study included 117 adults: 80 asymptomatic HTLV-1 carriers, including 51 with presumed vertical/breastfeeding transmission and 29 with presumed sexual transmission; 21 patients with ATLL; and 16 healthy controls. Peripheral blood mononuclear cells were analyzed by multiparameter flow cytometry. Total CD4 + T-cell frequency was measured among viable CD3 + T cells, while naïve, T memory stem cells (TSCM), central memory T cells (TCM), effector memory T cells (TEM), and terminally differentiated effector T cells (TTE) were defined within viable CD3 + CD4+ T cells using CD45RA, CCR7, and CD95. Group comparisons used Kruskal–Wallis tests followed by Dunn’s tests with Holm adjustment. False-discovery-rate correction was applied across six outcomes, and median regression estimated age- and sex-adjusted differences. Total CD4 + T-cell frequency showed a nominal difference among groups ( p = 0.0478) that did not remain significant after false-discovery-rate correction or covariate adjustment. Patients with ATLL had lower median naïve-cell frequencies than asymptomatic carriers and healthy controls (2.91% vs. 27.95% and 24.40%), lower TCM frequencies (12.30% vs. 25.35% and 31.85%), and higher TEM frequencies (49.80% vs. 16.15% and 17.80%). All three global comparisons remained significant after false-discovery-rate correction. After adjustment for age and sex, ATLL remained associated with lower naïve-cell frequencies versus asymptomatic carriers and healthy controls (− 25.00 and − 21.29% points), lower TCM frequencies (− 12.80 and − 16.97), and higher TEM frequencies (+ 34.40 and + 31.85), respectively. TSCM showed no significant unadjusted global difference, and TTE did not differ among groups. No statistically detectable immunophenotypic differences were identified between the presumed vertical/breastfeeding and sexual transmission groups. ATLL was associated with contraction of the naïve and TCM compartments and expansion of TEM cells, independently of age and sex. This pattern reflected differences in the relative distribution of circulating differentiation states rather than a consistent increase in total CD4 + T cells. Presumed transmission route was not associated with CD4 + T-cell subset distribution in asymptomatic carriers.