Search

Between January 1985 and December 1987, 5 out of 109 cadaver‐kidney transplant recipients developed an algodystrophy involving knees and ankles. Pain hindering movements occurred during the 3rd month following transplantation. Radiographic findings demonstrated epiphysical demineralization and bone‐scanning revealed increased uptake of a radioisotope in the affected joints. Calcium and parathormone levels were either normal or subnormal. Recovery was always achieved after calcitonin or griseofulvin therapy. Different factors possibly promote the occurrence of this pathology: preexistent renal osteodystrophy with secondary hyperparathyroïdism and pelvis surgery might have played underlying but not determinant roles with regard to the 500 patients who underwent kidney transplantation before January 1985 and who never experienced algodystrophy. The only difference between the two groups of patients was the introduction of cyclosporin‐A therapy after 1985. We suggest that this drug might contribute to the onset of algodystrophy by its vasoconstrictive action on the peripheral vessels, by its neurotoxicity and/or by an increased bone‐remodelling effect.

Induction of proliferation and differentiation in response to the addition of recombinant human granulocyte colony-stimulating factor (G- CSF) was studied by both suspension and semisolid cultures in a series of acute myeloid leukemias (AML). Induction of proliferation by G-CSF alone was observed in six of 27 cases of AML. All acute promyelocytic leukemias with the specific chromosomal translocation t(15;17) and one case of myelomonocytic leukemia with balanced chromosomal translocation involving chromosome 17 at band q12q21 were induced to proliferate strongly by the G-CSF. However, contrary to the long-term proliferative effect observed with granulocyte/macrophage colony-stimulating factor (GM-CSF), G-CSF activity can be characterized by its capability to initiate and promote the growth of responding AML cells but not to sustain long-term proliferation. Finally, no terminal differentiation was found, as assessed by morphology, cytochemistry, and cell surface marker analysis. These results indicate that G-CSF may be sufficient to provide a specific signal for induction of a transient proliferation in AML without induction of terminal differentiation. The cells with the highest response are clonal leukemia cells, all bearing a translocation involving the chromosome region 17q12q21 in which the G-CSF gene has been recently located.

We evaluated serially by cytogenetics the blood and marrow chimerism of 38 leukemic recipients of HLA-matched bone marrow transplants (BMT) who were prepared by high doses of alkylating agents and fractionated total- body irradiation (2.2 Gy X 5). Donor or host mitoses were identified by examination of sex chromosomes in 32 patients or by evaluation of the polymorphism of other chromosomes after specific banding in six patients. Twenty-four patients were recipients of untreated BMT, and 14 were recipients of T-cell-depleted BMT. In the 24 patients who received untreated BMT, all showed successful engraftment, and only three had a transient mixed chimera. In the 14 recipients of T-cell-depleted BMTs, four rejected their grafts, and seven had mixed chimeras; these mixed chimeras were more frequent in blood lymphocytes than in marrow cells and could be detected up to 26 months after BMT. This high frequency of partial chimerism after T-cell-depleted BMT by comparison with a control group suggests that the donor's T cells play an important role in the eradication of host residual hematopoiesis after allogeneic BMT.

Interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta) are two biochemically distinct, but distantly related, polypeptidic cytokines that play a key role in inflammation, immunologic reactions, and tissue repair. Recently, it has been shown that IL-1 alpha is identical to hematopoietin 1, which was described as a hematopoietic growth factor acting on early progenitor cells in synergy with other hematopoietic growth factors. In this report we discuss our use of in situ hybridization on human prometaphase cells with a human IL-1 alpha cDNA probe to localize the human IL-1 alpha gene on the proximal part of the long arm of chromosome 2 at band q13, in the same chromosomal region as the IL-1 beta gene.

Serial cytogenetic studies were performed on 60 leukemic recipients of HLA-matched bone marrow transplants (BMT) who were prepared by high doses of alkylating agents and fractionated total body irradiation (TBI). Forty-three patients were recipients of untreated BMT and 17 were recipients of T-depleted BMT. Donor or host mitoses were identified by examination of sex chromosomes in 54 patients or by evaluation of the polymorphism of other chromosomes after specific banding in six patients. Mixed lymphoid chimerism (MLC) was identified in 29 patients and full donor lymphoid chimerism (FDLC) in 29 patients. Complete donor hematopoiesis was recovered in most patients after 12 months, but two T-depleted patients had persistent host cells at 46 and 52 months after the graft. Acute graft-versus-host disease was significantly less frequent in patients with MLC, especially when more than 10% of residual lymphoid cells were detected. The probability of relapse and survival was identical in patients with MLC and FDLC, except in patients with chronic myeloid leukemia where MLC was significantly associated with an increased risk of relapse.

The capacity of the rabies virus superantigen (SAg) and the nucleocapsid (NC) to activate human tonsil lymphocytes was analyzed by studying the capacity of NC to cause lymphocytes to proliferate and secrete Ig and cytokines. NC activation was compared to that obtained with the Staphylococcus-derived SAg, SEE, and TSST-1. Despite a weak T lymphocyte mitogenic activity restricted to CD4⁺ T cells, NC triggers tonsil B lymphocytes to produce IgG in quantities and frequencies similar to those of SEE and TSST-1. In the same way as these two SAg, NC induces IgG production only in the presence of T cells and optimally with a T/B ratio of 1/5. However, unlike SEE and TSST-1, NC does not trigger IgM production. The pattern of cytokines produced upon NC activation, IL-4 and IL-10, weak IL-2 production, and no IFN-γ, suggests that rabies SAg stimulates Th2 rather than Th1 lymphocytes. In contrast, the pattern of cytokines produced upon TSST-1 activation, 1L-2, IFN-γ, and no IL-4, suggests that TSST-1 induces rather a Th1 response. The specific Th2 triggering by NC could explain the unique capacity of the rabies SAg to increase the in vivo antibody response to a simultaneously injected antigen. Copyright 1995, 1999 Academic Press

Recently we reported evidence that nucleocapsid (NC) of rabies virus is a Vbeta8-specific exogenous superantigen (SAg) in humans and a Vbeta6-specific SAg in BALB/c mice. NC was also found to stimulate rabies vaccination by enhancing the rabies neutralizing antibody response. In this study, we tested the hypothesis that the stimulating effect of NC and its SAg properties are linked. To do this, we studied the effect of rabies SAg on the immune response to an unrelated antigen, the influenza virus, and compared the response in two congenic strains of mice, BALB/c and BALB/D2. BALB/c mice are rabies SAg responsive, whereas BALB/D2 mice are not responsive to SAg activation by rabies NC because they lack the SAg recognition element, the Vbeta6 T cell receptor. In BALB/c mice, coinjection of rabies SAg with inactivated influenza virus resulted in a rapid and long-term increase in (a) the titres of influenza virus-specific antibodies (IgG and IgM), including protective hemagglutination-inhibiting antibodies, (b) antigen-specific proliferation and, (c) IL-2 and IL-4 secretion by lymph node lymphocytes, when compared to mice that received influenza virus only. In contrast, in BALB/D2 mice, neither antibody nor lymphocyte responses were stimulated. Moreover, during establishment of the primary response, the increase in influenza-primed T cells was mainly restricted to those bearing a Vbeta6 TCR. These data establish that rabies SAg can stimulate both T and B cell-specific responses to an unrelated antigen, depending on expression of the SAg target (Vbeta6 T lymphocytes). This is the first report linking NC adjuvant properties with its SAg mechanism.

The polymerase chain reaction was used to evaluate minimum residual disease in chronic myelogenous leukaemia (CML) patients after bone-marrow transplantation, by amplification of the transcript of the specific bcr/ablhybrid gene. Strict precautions were taken to avoid contamination. Peripheral blood cells from 22 patients transplanted for haematological malignant disorders were analysed. The results were clearcut for positive controls (patients with CML in relapse) and negative controls (patients with malignant disorders other than CML). In 11 of 12 CML patients in clinical and cytogenetic remission the bcr/abltranscript was detected 3 months to 6 years after transplantation. Thus, it appears that cells expressing the bcr/ablmRNA are not eradicated from the blood of CML patients in complete clinical remission even years after bone-marrow transplantation.

Serial cytogenetic studies were performed on 60 leukemic recipients of HLA-matched bone marrow transplants (BMT) who were prepared by high doses of alkylating agents and fractionated total body irradiation (TBI). Forty-three patients were recipients of untreated BMT and 17 were recipients of T-depleted BMT. Donor or host mitoses were identified by examination of sex chromosomes in 54 patients or by evaluation of the polymorphism of other chromosomes after specific banding in six patients. Mixed lymphoid chimerism (MLC) was identified in 29 patients and full donor lymphoid chimerism (FDLC) in 29 patients. Complete donor hematopoiesis was recovered in most patients after 12 months, but two T-depleted patients had persistent host cells at 46 and 52 months after the graft. Acute graft-versus-host disease was significantly less frequent in patients with MLC, especially when more than 10% of residual lymphoid cells were detected. The probability of relapse and survival was identical in patients with MLC and FDLC, except in patients with chronic myeloid leukemia where MLC was significantly associated with an increased risk of relapse.

Attenuated and highly neurovirulent rabies virus strains have distinct cellular tropisms. Highly neurovirulent strains such as the challenge virus standard (CVS) are highly neurotropic, whereas the attenuated strain ERA also infects nonneuronal cells. We report that both rabies virus strains infect activated murine lymphocytes and the human lymphoblastoid Jurkat T-cell line in vitro. The lymphocytes are more permissive to the attenuated ERA rabies virus strain than to the CVS strain in both cases. We also report that in contrast to that of the CVS strain, ERA viral replication induces apoptosis of infected Jurkat T cells, and cell death is concomitant with viral glycoprotein expression, suggesting that this protein has a role in the induction of apoptosis. Our data indicate that (i) rabies virus infects lymphocytes, (ii) lymphocyte infection with the attenuated rabies virus strain causes apoptosis, and (iii) apoptosis does not hinder rabies virus production. In contrast to CVS, ERA rabies virus and other attenuated rabies virus vaccines stimulate a strong immune response and are efficient live vaccines. The paradoxical finding that a rabies virus triggers a strong immune response despite the fact that it infects lymphocytes and induces apoptosis is discussed in terms of the function of apoptosis in the immune response.

We evaluated serially by cytogenetics the blood and marrow chimerism of 38 leukemic recipients of HLA-matched bone marrow transplants (BMT) who were prepared by high doses of alkylating agents and fractionated total-body irradiation (2.2 Gy x 5). Donor or host mitoses were identifled by examination of sex chromosomes in 32 patients or by evaluation of the polymorphism of other chromosomes after specific banding in six patients. Twenty-four patients were recipients of untreated BMT. and 1 4 were recipients of T-cell-depleted BMT. In the 24 patients who received untreated BMT. all showed successful engraftment. and only three had a transient mixed chimera. In the 14 recipients of T-cell-depleted BMTs. four rejected their grafts. and seven had mixed chimeras; these mixed chimeras were more frequent in blood lymphocytes than in marrow cells and could be detected up to 26 months after BMT. This high frequency of partial chimerism after Tcell- depleted BMT by comparison with a control group suggests that the donor’s T cells play an important role in the eradication of host residual hematopoiesis after allogeneic BMT.

Oncogenic activation of the MCF.2 cell line-derived transforming sequence gene (MCF2) occurs through substitution of part of its 5’ coding region by unrelated nonsyntenic sequences. Analysis of the MCF2 oncogene locus revealed complex recombination events involving four discontinuous human DNA segments. The upstream replacing sequence, named URS, represents the farthest 5’ portion of the locus. The URS sequence maps to the D15S93 locus on human chromosome 15q15→q23.