DNT cells

DNT cells (double-negative T cells) are a rare subpopulation of mature T lymphocytes characterized by the expression of CD3 and the absence of both CD4 and CD8 surface markers. They may express either αβ or γδ T-cell receptors. DNT cells constitute approximately 1–5% of peripheral blood T lymphocytes in healthy individuals. Their functions are diverse and context-dependent, including immunoregulatory/suppressive roles (such as preventing graft-versus-host disease and autoimmunity), as well as pro-inflammatory or cytotoxic activities in certain settings. In cancer therapy—particularly for acute myeloid leukemia (AML)—allogeneic DNT cell therapy is being developed as an adoptive cellular immunotherapy. These donor-derived DNTs can target leukemic blasts without inducing graft-versus-host disease, acting through mechanisms such as TNFα secretion that upregulates ICAM-1 on AML targets via a JAK1-dependent pathway, facilitating cytotoxicity through engagement with lymphocyte function-associated antigen 1 (LFA-1). In addition to direct anti-leukemic effects, DNTs can modulate other immune cell populations and have been shown to synergize with conventional donor-derived T-cells to enhance anti-leukemia activity while suppressing GvHD-inducing responses. DNT cell therapies are currently under investigation in early-phase clinical trials for relapsed/refractory AML post-allogeneic hematopoietic stem cell transplantation[6][8][10]. The University Health Network has sponsored at least one phase I trial using allogeneic double-negative T-cell products.

Other names

double-negative T cellsCD3+CD4−CD8− T cellsDN T cells