Functional double‐negative T cells in the periphery express T cell receptor Vβ gene products that cause deletion of single‐positive T cells

A proportion of peripheral T cells lack surface expression of the CD4 or CD8 coreceptor molecules and hence are designated as “double negative” (DN). Most DN T lymphocytes express the Γ/β T cell receptor (TcR), but a minor fraction of them, in both humans and mice, express the α/β TcR. Whereas α/β+ DN T lymphocytes are infrequent (< 1%) in conventional lymphoid organs (spleen, blood, lymph node), they account for two‐thirds of the T cells residing in adult bone marrow. Analysis of the TcR Vβ repertoire expressed by peripheral DN T cells revealed a high frequency of cells bearing autoreactive TcR that cause deletion of “single‐positive” (SP) (CD4+CD8− or CD4−CD8+) T cells. Peripheral DN cells thus represent a cell type that is relatively resistant to clonal deletion. Furthermore, such cells have not been inactivated (anergized) in vivo since they proliferate and secrete interleukins in response to cross‐linking by monoclonal antibodies specific for these Vβ gene products that are deleted in SP T cells. These results might help to understand the association of peripheral expansion of DN cells and development of autoimmune diseases.