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 V beta 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 V beta gene products that are deleted in SPT cells. These results might help to understand the association of peripheral expansion of DN cells and development of autoimmune diseases.
Martínez
C
C
Centro de Biologá Molecular, CSIC, Universidad Autónoma, Madrid, Spain.
Marcos
M A
MA
de Alboran
I M
IM
Alonso
J M
JM
de Cid
R
R
Kroemer
G
G
Coutinho
A
A
D000818:Animals; D017252:CD3 Complex / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis*; D016827:CD8 Antigens / Q000032:analysis*; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D013601:T-Lymphocytes / Q000276:immunology*
D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta