T-cell mitochondrial dysfunction and lymphopenia in DOCK2-deficient patients

To the Editor: Dedicator of cytokinesis 2 (DOCK2) is a guanine nucleotide exchange factor expressed predominantly in hematopoietic cells that activates the Rac GTPases.1,2 Biallelic mutations in DOCK2 cause a combined immunodeficiency with T-cell lymphopenia and impaired T-cell activation.1,3 The mechanisms underlying the T-cell lymphopenia associated with DOCK2 deficiency are incompletely understood. Because of the importance of the Rac GTPases in maintaining mitochondrial homeostasis,4,5 we investigated mitochondrial function in 2 unrelated patients with novel DOCK2 mutations abrogating protein expression. [...]to our DOCK2-deficient patients, CD4+ and CD8+ T cells robustly increased membrane potential after T-cell activation (see Fig E1). [...]chronic antigenic T-cell activation cannot solely explain the defective mitochondrial membrane potential seen in DOCK2-deficient T cells. Because Patient 1 had normal numbers of B cells, we were able to generate an EBV-transformed lymphoblastoid B-cell line (BLCL) from her PBMCs.