Expression of CD28 is highly regulated during thymic development, with CD28 levels extremely low on immature thymocytes but increasing dramatically as CD4- CD8- cells initiate expression of TCRbeta. B7-1 and B7-2, the ligands for CD28, have a restricted distribution in the thymic cortex where immature thymocytes reside and are more highly expressed in the medulla where the most mature thymocyte...

CD6, a 130-kDa surface glycoprotein, is expressed primarily on cells of T lineage. A co-stimulatory role for CD6 in mature T cells has been shown, but the function of CD6 during thymocyte development is unknown. Since CD6 ligands are expressed on thymic epithelium, their interactions with CD6 could be important in thymic selection. In this report we show that CD6 is developmentally regulated in...

The role of the thymus in induction of leukemia was studied in vitro. Curltivation of normal thymus cells on thymus epithelial reticulum cell monolayers that had been grown from radiation leukemia virus-induced leukemic thymuses rendered the thymocytes leukemic. C57BL/6 thymocytes were cultivated for 3 days on leukemic thymus reticulum monolayers, and 106 thymocytes were injected i.p. into youn...

SOCS1 / mice die prematurely of increased interferon(IFN ) signaling with severe thymic atrophy and accelerated maturation of T cells. However, it was unclear whether the thymic defects were caused by SOCS1 deficiency or by increased IFN signaling. Using SOCS1 / IFN / mice, we show in this study that SOCS1 deficiency skews thymocyte development toward CD8 lineage independently of IFN . Fetal th...

It has recently been shown that CD4(+)CD25(+) T cells are immunoregulatory T cells that prevent CD4(+) T-cell-mediated organ-specific autoimmune diseases. In this study, the regulatory mechanism of CD4(+)CD25(+) T-cell development were investigated using T-cell receptor (TCR) transgenic mice. It was found that CD4(+)CD25(+) T cells preferentially expressed the endogenous TCRalpha chain in DO10(...

The effect of physiological and pharmacologically induced thymus involution was studied in 12-week-old female C57BL mice. Thymus involution was estimated by measurement of the thymus weight and the ability of thymocytes to induce a graft-versus-host (GvH) reaction at 48 h after delivery or drug administration in comparison with control (virgin, saline-treated) mice. The thymus weight and immuno...

CD1d-dependent invariant Valpha14 (Valpha14i) NKT cells are innate T lymphocytes expressing a conserved semi-invariant TCR, consisting, in mice, of the invariant Valpha14-Jalpha18 TCR alpha-chain paired mostly with Vbeta8.2 and Vbeta7. The cellular requirements for thymic positive and negative selection of Valpha14i NKT cells are only partially understood. Therefore, we generated transgenic mic...

Interaction of the T cell receptor (TCR) with peptide/major histocompatibility complexes (MHC) in the thymus is of critical importance for developing thymocytes. In a previous study, we described an antagonist peptide that inhibited negative selection of transgenic thymocytes induced by an agonist peptide. In this study we show that this antagonist peptide can induce positive selection of CD8(+...

BMP2/4 signaling is required for embryogenesis and involved in thymus morphogenesis and T-lineage differentiation. In vitro experiments have shown that treatment of thymus explants with exogenous BMP4 negatively regulated differentiation of early thymocyte progenitors and the transition from CD4-CD8- (DN) to CD4+CD8+ (DP). Here we show that in vivo BMP2/4 signaling is required for fetal thymocy...

An examination of thymocytes and peripheral T cells from SHP-1-deficient motheaten mice possessing a transgenic MHC class I-restricted TCR has implicated SHP-1 in regulating TCR signaling thresholds at three checkpoints in T cell development and activation. First, in the population of CD4-CD8- double negative thymocytes, SHP-1 appears capable of regulating signals from TCR complexes that contro...