Significant involvement of nuclear factor-κB-inducing kinase in proper differentiation of αβ and γδ T cells.

Nuclear factor-κB-inducing kinase (NIK) is known to play a critical role in maintaining proper immune function. This is exemplified in the spontaneous mutant mouse lacking functional NIK, alymphoplasia (aly), which is simultaneously immune-compromised and autoimmune-prone. To investigate the role of NIK in αβ T-cell repertoire formation, we analysed T-cell development in aly/aly mice bearing a transgenic T-cell receptor (TCR).

Ectopic expression of a T-box transcription factor, eomesodermin, renders CD4(+) Th cells cytotoxic by activating both perforin- and FasL-pathways.

During viral infection, CD8(+) cytotoxic T lymphocytes (CTL) play a central role to eliminate viruses by destructing virus-infected cells utilizing two cytolytic pathways, i.e., perforin/granzyme pathway and FasL-Fas pathway.

Cognate interaction plays a key role in the surveillance of autoreactive B cells in induced mixed bone marrow chimerism in BXSB lupus mice.

The effects of bone marrow transplantation (BMT) as a treatment for and/or preventive measure against autoimmune diseases in mice were investigated extensively. The reconstitution of the hematopoietic system with a mixture of autologous and heterologous bone marrow cells was reported to suppress the development of autoimmune diseases. However, the pathological mechanism through which mixed chimerism results in the suppression of disease development is still unknown.

Accumulation of allo-MHC cross-reactive memory T cells in bone marrow.

The T cells in the bone marrow (BM) have recently been shown to be enriched with memory T cells. We investigated in this study the reactivity of minor-antigen specific memory cytotoxic T lymphocytes (CTLs) induced from the BM of in vivo primed mice using two different antigen systems. The antigen-specific CTLs could be efficiently induced from the BM of immunized mice.

Development of immunocompetent lymphocytes in vivo from murine umbilical cord blood cells.

Background: Reports concerning the immunological functions of lymphocytes derived from umbilical cord blood cell (UCBC) have been limited.

Methods: In murine syngeneic transplantation system using green fluorescent protein transgenic donors, UCBC-derived lymphocytes were studied for their immunological competence.

Results: Hematopoietic stem cells (HSC) among UCBC differentiated in the recipients into phenotypically mature T and B lymphocytes.

A human mutant CD4 molecule resistant to HIV-1 binding restores helper T-lymphocyte functions in murine CD4-deficient mice.

CD4 is a cell surface glycoprotein that acts as a co-receptor for the T cell antigen receptor by binding to a non-polymorphic portion of MHC molecules. CD4 also functions as a receptor for human immunodeficiency virus type-I (HIV-1) because the viral envelope glycoprotein gp120 binds to CD4 with a high affinity. We have previously demonstrated that introduction of mutations into CD4 abolished the binding of gp120 and prevented HIV-1 from entering cells and spreading.

Cross-positive selection of thymocytes expressing a single TCR by multiple major histocompatibility complex molecules of both classes: implications for CD4+ versus CD8+ lineage commitment.

This study has investigated the cross-reactivity upon thymic selection of thymocytes expressing transgenic TCR derived from a murine CD8+ CTL clone. The Idhigh+ cells in this transgenic mouse had been previously shown to mature through positive selection by class I MHC, Dq or Lq molecule. By investigating on various strains, we found that the transgenic TCR cross-reacts with three different MHCs, resulting in positive or negative selection.

Prominent dominant negative effect of a mutant Fas molecule lacking death domain on cell-mediated induction of apoptosis.

Using a panel of transfectant B lymphoma cells expressing varying amounts of the mutant Fas together with the endogenous wild type Fas, semi-quantitative studies on the dominant negative effect of a murine mutant Fas molecule lacking death domain were carried out. In anti-Fas antibody-mediated induction of apoptosis, the mutant molecules exerted significant dominant-negative effect only when their expression level was comparable to or higher than that of wild type molecules, or when exposed to low amounts of the antibody. The inhibitory effect was accompanied by the failure in DISC formation in spite of Fas aggregation.

Full reconstitution of hematopoietic system by murine umbilical cord blood.

Background: Murine umbilical cord blood cells (UCBCs) were studied for their ability to reconstitute the hematopoietic system.

Methods: On average, 150 microL of cord blood per fetus containing 1.2 to 2 x 10(4) nucleated cells were collected from day 18.

Cell-mediated fas-based lysis of dendritic cells which are apparently resistant to anti-Fas antibody.

In this report, the controversy concerning the sensitivity of dendritic cells (DCs) to Fas-dependent induction of apoptosis was examined using murine DCs. Although DCs could not be lysed when exposed to an anti-Fas antibody, Jo2, the observed resistance turned out to reflect their lack of the expression of Fc(gamma)R necessary for crosslinking the antibody, rather than their intrinsic resistance. Thus, at least a fraction of DCs was sensitive to Jo2 in the presence of Fc(gamma)R-expressing by-standers.

DNA immunization via intramuscular and intradermal routes using a gene gun provides different magnitudes and durations on immune response.

We investigated the antibody (Ab) and cytotoxic T lymphocyte (CTL) responses to gene gun (GG)-mediated DNA immunization via the intramuscular (i.m.) and intradermal (i.

Lack of evidence for aggregation-dependent enhancement of p56lck in the signal transduction upon major histocompatibility complex recognition by mature T cells.

The kinase activity of lymphocyte-specific tyrosine kinase p56lck (Lck) upon physiological major histocompatibility complex (MHC) recognition by normal mature T cells was examined. Recognition of the target MHC molecules by T cells induced phosphorylation of the zeta-chain without obvious enhancement of the background Lck activity. There was no sign of enhancement of Lck through putative T-cell receptor (TCR)-independent class II MHC/CD4 interactions either.