Targeted T-cell depletion or CD154 blockade generates mixed hemopoietic chimerism and donor-specific tolerance in mice treated with sirolimus and donor bone marrow.

Background: The administration of donor specific bone marrow (DSBM) to mice conditioned with antilymphocyte serum (ALS) and sirolimus can result in stable multilineage mixed chimerism and long-term graft survival. This study seeks to determine if either the targeted depletion of CD4 and/or CD8 pos T cells or costimulation blockade can substitute for ALS and preserve the efficacy of this regimen.

Methods: C57BL/6 recipients of BALB/c skin allografts were treated with DSBM (150 x 10(6) cells), sirolimus (24 mg/kg intraperitonealy), and either ALS or various monoclonal antibodies (alphaCD4, alphaCD8, alphaCD154 alone or in combination).

Association of cytokine polymorphic inheritance and in vitro cytokine production in anti-CD3/CD28-stimulated peripheral blood lymphocytes.

Background: Genetic variations in cytokine genes are thought to regulate cytokine protein production. However, studies using T cell mitogens have not always demonstrated a significant relationship between cytokine polymorphisms and in vitro protein production. Furthermore, the functional consequence of a polymorphism at position -330 in the IL-2 gene has not been described.

Efficient priming of protein antigen-specific human CD4(+) T cells by monocyte-derived dendritic cells.

Dendritic cells (DCs) have the unique ability to initiate an immune response in vivo by capturing antigens (Ags) in peripheral tissues and migrating to secondary lymphoid organs, where they sensitize naive CD4(+) T cells. To mimic this process in vitro, previous studies have shown that DCs directly isolated from peripheral blood can be used to elicit primary responses to neoantigens (neoAgs). In other studies, when monocyte-derived DCs have been utilized to sensitize total CD4(+) T cells in vitro, only secondary proliferation to neoAgs could be elicited.

Costimulatory molecules are active in the human xenoreactive T-cell response but not in natural killer-mediated cytotoxicity.

Background: T-cell costimulatory blocking agents inhibit allospecific T-cell responses in vitro and prevent allograft rejection in vivo. Costimulatory requirements for discordant xenospecific cellular responses remain undefined. We have evaluated costimulatory molecule expression by porcine endothelial cells (PEC) after interaction with human cells and tested agents known to inhibit allospecific responses for their ability to inhibit xenospecific responses in vitro.