FUNCTIONAL DOUBLE-NEGATIVE T-CELLS IN THE PERIPHERY EXPRESS T-CELL RECEPTOR V-BETA-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 gamma/delta T cell receptor (TcR), but a minor fraction of them, in both humans and mice, express the alpha/beta TcR. Whereas alpha/beta+ 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 Vbeta 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 Vbeta 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.