When stimulated for a few days with the mitogenic GT2 + T11(1) CD2 mAb pair and IL-2, resting T cells were induced to proliferate but the introduction into the cultures of a third CD2 mAb resulted in apoptotic cell death of 40 to 60% of the cells. The death signal was active on T cells entered the cell cycle without causing an apparent cell cycle block and without discriminating between the G1 and S phases. Apoptosis was not prevented by cycloheximide or actinomycin D, indicating that the death program was already expressed in preactivated cells awaiting an appropriate signal. A series of Abs, directed at various cell surface molecules, were unable to trigger apoptosis (except CD3 mAb), whereas most of the CD2 mAb tested were active, provided the third CD2 mAb was recognizing an epitope different from GT2 and T11(1). Mere aggregation of CD2 molecules did not seem to be the triggering signal of apoptosis, because cross-linking cell-bound GT2 + T11(1) with an Ab to mouse IgG had no effect, suggesting that a conformational change was imposed on CD2 molecules by the third CD2 mAb. Stimulation performed in the presence of IL-2 predisposed both CD45R0+ and CD45RA+ T cells to apoptosis, whereas stimulation in the presence of IL-4 primed only CD45RA+ T cells to undergo this process. Monocytes and potent co-signals of the CD2 pathway were unable to prevent CD2-induced apoptosis. Thus, successive engagements of the CD2 molecule of mature T cells by two and three CD2 mAbs recognizing distinct epitopes can provide in short term cultures signals for proliferation and apoptosis, depending on the activation state of the cells.

Antibodies, Monoclonal↗

PubMed1994

[Generalities on immunological mechanisms of graft rejection].

Explore the source record for details and available documents.

Graft Rejection↗

PubMed1994

Effect of plasma protein adsorption on protein excretion in kidney-transplant recipients with recurrent nephrotic syndrome.

BACKGROUND: Among patients with the idiopathic nephrotic syndrome who have focal and segmental glomerulosclerosis and undergo renal transplantation, 15 to 55 percent have recurrent nephrotic syndrome. The recurrence may be caused by a plasma factor or factors that increase glomerular permeability, because plasma exchange transiently decreases or abolishes proteinuria in some patients. We studied the effect on proteinuria of the removal of protein (mostly immunoglobulins) by adsorption onto protein A from the plasma of patients with recurrent nephrotic syndrome. METHODS: Eight patients were treated with one to three cycles of two to seven 1-day sessions of protein adsorption, and the patients' urinary protein excretion was measured repeatedly. Their immunosuppressive regimens were not changed during the treatment. The adsorbed proteins were eluted from the protein A and injected into rats, and the urinary albumin excretion of the rats was measured. RESULTS: The protein-adsorption treatment consistently decreased urinary protein excretion by an average of 82 percent at the end of a cycle (P < 0.001). In one patient proteinuria disappeared, and in another urinary protein excretion remained below 2.5 g per day with repeated cycles of protein adsorption. In all but one patient the effect of adsorption was limited in time, with a return to the preadsorption level of protein excretion within a maximum of two months. The administration to rats of material eluted from the protein A increased urinary albumin excretion 2.9- to 4.6-fold (P < 0.001 and P = 0.005, respectively). Although protein A primarily binds immunoglobulins, the active fraction of the eluted proteins had a molecular weight below 100,000, indicating that immunoglobulin was not directly involved. CONCLUSIONS: Adsorption of plasma protein decreases urinary protein excretion in patients with recurrence of the nephrotic syndrome after renal transplantation. Studies of the adsorbed proteins should provide information about the mechanism of this disease.

Adolescent↗

PubMed1994

The Escherichia coli gapA gene is transcribed by the vegetative RNA polymerase holoenzyme E sigma 70 and by the heat shock RNA polymerase E sigma 32.

Escherichia coli D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is produced by the gapA gene and is structurally related to eukaryotic GAPDHs. These facts led to the proposal that the gapA gene originated by a horizontal transfer of genetic information. The yields and start sites of gapA mRNAs produced in various fermentation conditions and genetic contexts were analyzed by primer extension. The transcriptional regulatory region of the gapA gene was found to contain four promoter sequences, three recognized by the vegetative RNA polymerase E sigma 70 and one recognized by the heat shock RNA polymerase E sigma 32. Transcription of gapA by E sigma 32 is activated in the logarithmic phase under conditions of starvation and of heat shock. Using a GAPDH- strain, we found that GAPDH production has a positive effect on cell growth at 43 degrees C. Thus, E. coli GAPDH displays some features of heat shock proteins. One of the gapA promoter sequences transcribed by E sigma 70 is subject to catabolic repression. Another one has growth phase-dependent efficiency. This complex area of differentially regulated promoters allows the production of large amounts of gapA transcripts in a wide variety of environmental conditions. On the basis of these data, the present view of E sigma 32 RNA polymerase function has to be enlarged, and the various hypotheses on E. coli gapA gene origin have to be reexamined.

Amino Acid Sequence↗

PubMed1994

Incidence of vascular complications in kidney transplantation: is there any interference with the nature of the perfusion solution?

Two non-randomized groups of 100 kidney transplants each were compared in relation to the flush-out solution used. The two groups were similar with the exceptions of the number of multiple artery kidneys and the proportion of kidneys procured in our center. The rate of vascular complications such as arterial venous thrombosis and renal artery stenosis was higher in the Eurocollins (19) group than in the UW group (4) p < 0.01, even if the multiple artery kidneys are excluded. These results need to be confirmed by a randomized study but it is clear that the use of the UW solution leads to a better arterial flow with fewer vascular complications.

Adenosine↗

PubMed1994

[Immunoadsorption of anti-HLA antibodies on protein A-sepharose columns in hyperimmunized recipients waiting for transplantation].

In an attempt to reduce anti-HLA immunization in 15 patients awaiting for renal grafts and who were immunized against 65% of a panel of lymphocytes (titre 1/8 to 1/128), were given 5 to 7 sessions of immunoadsorption on protein A columns, immunosuppressor drugs (corticosteroids: 1 mg/kg/day + cyclophosphamid: 2 mg/kg/day) and intravenous polyclonal immunoglobulins. The antibody titres decreased in all patients, but this protocol did not sufficiently block resynthesis of antibodies. Among the 12 patients who were transplanted, the graft functioned correctly in 8 after a follow-up of 3 months to 3 years. Three early graft failures occurred in the group of 5 patients whose had had a positive cross-match before treatment. This treatment did not appear to increase the frequency of infectious complications immediately after transplantation.

Adult↗