Requirement of dendritic cells and B cells in the clonal deletion of Mls-reactive T cells in the thymus.
The present study was performed to identify cells responsible for the elimination of T cells reactive with minor lymphocyte-stimulating (Mls) antigens during T cell development. Experiments were carried out in a fetal thymus organ culture (FTOC) system. To examine the tolerance-inducing activity, various populations of cells from adult CBA/J (Mls-1a) mice were injected into deoxyguanosine (dGuo)-treated FTOC of C3H/He (Mls-1b) mice with a microinjector, and 2 d later, the thymus lobes were injected with fetal thymus cells from C3H/He mice as T cell precursors. After 14 d of cultivation, cells were harvested and assayed for the expression of the T cell receptor V beta 6 element. The absence or marked reduction of T cells expressing V beta 6 at high levels (V beta 6high) was regarded as indicating the deletion of Mls-1a-reactive T cells. T cell-depleted populations of thymic as well as splenic cells from CBA/J mice were able to induce clonal deletion. Further characterization of the effector cells was carried out by fractionating the spleen cells before injecting them into dGuo-FTOC. None of the dish-adherent population, dish-nonadherent population, or purified B cells alone were able to induce clonal deletion, whereas the addition of purified B cells to adherent cells restored tolerance inducibility. It was further shown that a combination of CBA/J B cells and C3H/He dendritic cells was effective in eliminating Mls-reactive clones. These results indicate that for the deletion of clones reactive with Mls antigens during T cell development in the thymus, both DC and B cells are required.
Mazda
O
O
Department of Immunology, Kyoto University, Japan.
Watanabe
Y
Y
Gyotoku
J
J
Katsura
Y
Y
D000818:Animals; D000954:Antigens, Surface / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002448:Cell Adhesion; D003713:Dendritic Cells / Q000276:immunology*; D005333:Fetus; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D016747:Minor Lymphocyte Stimulatory Antigens; D009924:Organ Culture Techniques; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
D000954:Antigens, Surface; D016747:Minor Lymphocyte Stimulatory Antigens; D011948:Receptors, Antigen, T-Cell