Efficient direct priming of tumor-specific cytotoxic T lymphocyte in vivo by an engineered APC.

Although numerous studies have documented a role for B7-1 (CD80) in the induction of antitumor CTL immunity, it is presently unclear to what extent expression of this costimulatory molecule truly endows tumors with significant in vivo APC (antigen-presenting cell) capacity. Recent studies have, in fact, demonstrated that cross-priming, rather than direct priming, may constitute the major mechanism of CTL induction by B7-1 expressing tumors. We have, therefore, investigated the requirements for antigen density and costimulatory molecules in direct CTL priming with a prototype cell-based vaccine that uses a signal sequence-containing minigene to direct expression of a tumor-specific CTL epitope to the endoplasmic reticulum.

Missing T-cell receptor V beta families following blood transfusion. The role of HLA in development of immunization and tolerance.

Previously, we showed that donor-specific CTL nonresponsiveness occurs in transfused recipients sharing one HLA haplotype (or at least one HLA-B and one HLA-DR antigen) with the blood donor. The aim of the present study was to disclose the distinct effects of BT on the T-cell receptor repertoire and to analyze which factors determine the tolerizing versus immunizing properties of BT. We show here that recipients of HLA-sharing BT develop not only donor-specific CTL nonresponsiveness posttransfusion, but also a significant decrease in the usage of one to three V beta families as shown by PCR.

High-affinity cytotoxic T lymphocytes after non-HLA-sharing blood transfusion--the other side of the coin.

Previously, we have shown that pretransplantation blood transfusion modulates the T cell repertoire to a great extent. Patients receiving a BT from a donor sharing one HLA haplotype with the patient (HLA-sharing BT) develop CTL nonresponsiveness against cells of the BT donor and show a selective decrease in the usage of T cell receptor V beta families. The present study has focused on the analysis of the T cell repertoire in patients receiving an HLA mismatched (non-HLA-sharing) BT.

Pretransplantation blood transfusion revisited.

Background: Blood transfusion before organ transplantation has a beneficial effect on allograft survival; the mechanism of this effect has remained a mystery. In murine models, the presence of common histocompatibility antigens in the blood donor and the recipient favors the induction of allograft tolerance.

Methods: To investigate the effect of HLA compatibility between blood donor and recipient on the induction of allograft tolerance, we determined the relative frequency of cytotoxic T-lymphocyte precursors specific for donor cells before and at several times after blood transfusion in 23 patients awaiting a first renal transplant.

Different requirements for the regulation of transplantation tolerance induction for allogeneic versus xenogeneic major histocompatibility complex antigens.

One way to solve the problem of human donor organ shortage is the use of animal organs. Therefore, it is important to study the T-cell response against xenogeneic major histocompatibility complex (MHC) antigens. In the present study, we have used HLA-B27 transgenic mice in a xenogeneic transplantation model.

Induction of transplantation tolerance by intravenous injection of allogeneic lymphocytes across an H-2 class II mismatch. Different mechanisms operate in tolerization across an H-2 class I vs. H-2 class II disparity.

Previously, we have shown that the intravenous (i.v.) injection of allogeneic lymphocytes across an H-2 class I-mutant disparity leads to specific skin allograft tolerance caused by irradiation-sensitive donor T cells, which function as veto cells.

Allograft tolerance induction in adult mice associated with functional deletion of specific CTL precursors.

Rejection of H-2 class I bm 1 mutant skin allografts by B6 recipient mice is mediated by a population of CD8+ anti-bm1 cytotoxic T-lymphocytes that produces and consumes its own T helper factor in response to bm1 skin allografts (dual function CTL). Previously we have demonstrated that transfusion of allogeneic lymphocytes across an H-2 class I disparity induces specific long-lasting skin allograft survival. We now show that intravenous injection of allogeneic spleen cells across the bm1 mutant disparity results in a temporary decrease of donor-reactive CTLp in the spleen of recipient mice, lasting for approximately five weeks.

Mechanism of skin allograft enhancement across an H-2 class I mutant difference. Evidence for involvement of veto cells.

Intravenous injection of spleen cells across mutant class I H-2 incompatibility results in a drastic donor-specific prolongation of skin allograft survival and a marked decrease in the donor-specific cytotoxic T lymphocyte precursor (CTLp) frequency. This immunosuppressive effect depends on the presence of radiosensitive T cells in the donor cell inoculum. It was excluded that a graft-vs.

Inorganic pyrophosphate synthesis during methanogenesis from methylcoenzyme M by cell-free extracts of Methanobacterium thermoautotrophicum (strain delta H).

Cell-free extracts of Methanobacterium thermoautotrophicum (strain delta H) were found to contain high concentrations of inorganic pyrophosphate (up to 40 mM). The compound was accumulated by the organism despite high activity of inorganic pyrophosphatase which was found to be present in the cell extracts (1-2 mumol min-1 mg protein-1). This activity was strongly inhibited at [PPi] greater than 1.