Cytotoxic double-negative T cells, γδ, and MAIT cells are dysregulated in patients with telomere diseases. Patients with TBD exhibited alterations in minor subsets of T cells, namely double-negative T cells and unconventional T lymphocytes. Such imbalance was especially seen in MAIT cells, which are markedly reduced and activated in TBD. (A) Box plot of frequencies of double-negative T cells, defined as CD3⁺CD4^–CD8^–Vδ2^–CD45RA⁺CCR7^–Tbet⁺GZMB⁺. (B) Double-negative T cells, γδ, and MAIT cells are presented on viSNE maps for control and patient groups. (C) Percentage of Vδ2 γδ T cells in total CD3⁺ lymphocytes. (D) MAIT cells frequencies out of total CD3⁺ lymphocytes. (E) Additional flow cytometry was performed to assess the expression of HLA-DR and CD38 in CD3⁺CD161^hiVα7.2⁺ MAIT cells, as depicted for healthy controls and patients with TBD. (F-H) Box plots showing the percentages of expression of CD38 and HLA-DR in MAIT cells. (I) Spearman correlation between total circulating MAIT cells and their expression of CD38 and HLA-DR. ∗P ≤ .05; ∗∗P ≤ .01; ∗∗∗∗P ≤ .0001. DN, double negative; TBD, telomere biology disorder; t-SNE, t-distributed stochastic neighbor embedding.