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S Brouard

Publications and source records attributed to S Brouard.

33 records · Page 2Linked to original sources
PubMed1999

T cell receptor repertoire usage in allotransplantation: an overview.

Lymphocytes express antigen receptors that allow the immune system to specifically recognize antigens. In transplantation, T cells play a critical role in the rejection process, and different protocols inhibiting T cell-mediated alloreactivity efficiently achieve prolongation of allograft survival. T cells can interact with alloantigens by two ways, either by the "indirect" pathway that correspond to the physiological mechanism of T cell immune recognition, or through the "direct" pathway where they recognize alloantigens directly on the surface of donor cells. If some T cells are specifically activated in allorecognition, one should be able to indirectly detect this "selection" by analyzing the T cell receptor usage that could be biased and reflect the preferential amplification of alloreactive lymphocyte subsets. Nevertheless compared with disease states such as cancer or autoimmunity the T cell receptor repertoire is still largely uncharacterized. We review the current results available on T cell repertoire usage in transplantation studies involving humans or various animal models. The T cell receptor repertoire involved in transplantation (restricted or unrestricted) and the features potentially common to alloimmune responses will be discussed.

Animals↗
PubMed1999

Prolongation of heart xenograft survival in a hamster-to-rat model after therapy with a rationally designed immunosuppressive peptide.

BACKGROUND: Modification of the aminoacid sequence of peptides derived from the HLA class I heavy chain in combination with computer rational design resulted in the development of a peptide, RDP1258, with enhanced immunosuppressive activity. METHODS: We evaluated the activity of this peptide, analyzing infiltrate by immunohistology and cytokine transcripts by reverse transcriptase-polymerase chain reaction method, in a hamster-to-rat xenograft model where recipients were treated with cobra venom factor (CVF) and peptide. RESULTS: Although CVF or peptide alone had no effect, a combination of CVF/peptide RDP1258 resulted in a significant prolongation of graft survival (7.9+/-1 vs. 4.5+/-0 and 3.5+/-0 days, P<0.001). This effect was associated with an increased expression of heme oxygenase 1 (HO-1) in spleen, a significant reduced graft infiltrate, and a decrease of tumor necrosis factor-alpha mRNA transcripts (P<0.05) compared with CVF-treated recipients (1.6+/-0.07 vs. 3.3+/-0.3%, P=0.001) on day 3 after transplantation. CONCLUSION: These observations are consistent with the observation that up-regulation of HO-1 results in inhibition of immune effector functions and suggest that the peptide acts, at least partially, through HO-1 regulation.

Animals↗
PubMed1999

T cell repertoire alterations of vascularized xenografts.

The role of T cells in the rejection of vascularized xenografts has been little explored. Because of the high potential diversity of xenoantigens, it has been suggested that xenotransplantation could induce a strong cellular response that could contribute to delayed rejection. Alternatively, alterations in molecular interactions could impair the T cell response. Because the analysis of TCR repertoire in vivo indirectly reflects the nature and the magnitude of T cell xenorecognition, we took advantage of the possibility of obtaining long term survival of hamster heart xenografts in rat recipients treated with a combination of cobra venom factor and cyclosporin A (CsA), to analyze T cell infiltration and, for the first time, V beta TCR usage, at the complementarity-determining region 3 level, in accommodated and rejected xenografts, compared with allografts. After withdrawal of CsA (on day 40), the analysis of V beta family expression and corresponding complementarity-determining region 3 lengths in rejected xenografts revealed a Gaussian pattern, in contrast to a much more restricted pattern in rejected allografts (p = 0.002), suggesting that, after withdrawal of CsA, all the underrepresented T cell clones are rapidly expanded in xenografts. These results correlate with the rapid kinetics of rejection (4 +/- 1 days), the high number of T cells, the rapid expression of markers of activation (IL-2 receptor alpha-chain and class II receptor), and the strong deposit of IgG Abs in rejected xenografts. Taken together, these results suggest that the intensity and diversity of the T cell response to xenografts could be stronger than the response to allografts in vivo.

Animals↗
PubMed1999

T cell response in xenorecognition and xenografts: a review.

Xenotransplantation has recently become a subject of interest for the transplantation community due to the current organ shortage, which could be partially or even totally solved by the development of this strategy. The humoral response, which arises as a result of species disparities, is the major obstacle to the success of xenotransplantation. However, if the use of different strategies such as plasmapheresis, immunoadsorption, the utilization of organs from transgenic pigs for complement regulatory molecules and new immunosuppressive drugs, may allow to overcome or reduce the early antibody mediated rejections (hyperacute or acute vascular rejection), delayed responses based on cellular activations will still occur. In this review, despite the fact that different cell populations have been shown to be implicated in these phenomena (NK, granulocytes, macrophages), we will focus on recent published information concerning T cell response only, in xenorecognition.

Animals↗
PubMed1999

RDP1258, a new rationally designed immunosuppressive peptide, prolongs allograft survival in rats: analysis of its mechanism of action.

Peptides derived from the HLA class I heavy chain (a.a. 75-84) have been shown to modulate immune responses in vitro and in vivo in a non-allele-restricted fashion. In vivo studies in rodents have demonstrated prolonged allograft survival following peptide therapy. The immunomodulatory effect of these peptides has been correlated with peptide-mediated modulation of heme oxygenase 1 activity (HO-1). Recently, we used a rational approach for designing novel peptides with enhanced immunosuppressant activity. These peptides were also more potent inhibitors of HO-1 activity in vitro. Here we evaluated one of these peptides, RDP1258, for its ability to prolong heterotopic heart graft survival in rats. The peptide mediated effect on HO-1 was analyzed in vitro and in vivo. Peptide RDP1258 was shown to inhibit rat HO-1 in vitro in a dose-dependent fashion. However, RDP1258, like other HO-inhibitors, when administered to rats, secondarily resulted in an up-regulation of splenic HO-1 activity. Up-regulation of HO-1 was associated with prolonged heart allograft survival (6.6 +/- 0.6 vs. 2/14 > 100 days and 12/14 16.2 +/- 1.7 days; p < 0.001). The analysis of graft infiltrating cells on day 5 after transplantation showed a significant decrease in the number of graft infiltrating cells in RDP1258-treated recipients compared to untreated ones (14.8 vs. 32.7%; p < 0.01). In addition, grafts from peptide-treated animals showed significantly decreased expression of TNF-alpha mRNA and increased levels of iNOS mRNA. Our results are consistent with the recent observation that up-regulation of HO-1 results in the inhibition of several immune effector functions. Modulation of HO-1 activity may enable the development of novel immunomodulatory strategies in humans.

Adjuvants, Immunologic↗
PubMed1998

Critical requirement for graft passenger leukocytes in allograft tolerance induced by donor blood transfusion.

Tolerance to a vascularized allograft can be induced in adult animals by pregraft donor-specific blood transfusion (DST). Mechanisms underlying this effect appear to depend on unresponsiveness of alloreactive T-helper cells. In this study, we examined the roles of DST and cellular components of the allograft that are important in inducing T-cell unresponsiveness in a rat model. DST alone did not tolerize alloreactive recipient T-helper cells, but the combination of DST and heart allograft induced profound inhibition of the antidonor proliferative response in spleen but not in lymph node cells. When heart allografts were depleted of passenger leukocytes by pretreating the donor with cyclophosphamide or by parking the graft for 2 months in a tolerant recipient, tolerance induction in DST-treated recipients was abrogated. Tolerance could then be restored in a majority of DST-treated recipients of passenger leukocytes depleted grafts by injecting them at the time of grafting with donor, but not third-party, dendritic cells. This indicates that graft passenger leukocytes, most likely dendritic cells, are required for DST-induced allograft tolerance.

Animals↗
PubMed1998

Long-term survival of hamster-to-rat cardiac xenografts in the absence of a Th2 shift.

BACKGROUND: In hamster-to-rat cardiac xenografts, long-term survival (LTS) is obtained in 60% of recipients if vascular rejection is overcome by cobra venom factor and cyclosporine (CsA). It has been suggested that this accommodation state could be due to the Th2 response. METHODS: We examined the infiltrate by using immunostaining and the accumulation of cytokine mRNA (interferon-gamma [IFN-gamma], interleukin [IL]-4, IL-10, IL-13, and transforming growth factor-betal [TGF-beta1]) by using competitive reverse transcriptase polymerase chain reaction, in hamster hearts grafted into LEW.1A rat. RESULTS: Hearts from untreated and treated (cobra venom factor and CsA) but rejecting recipients presented a rapid and severe vascular rejection. In contrast, hearts from long-surviving treated animals had subnormal cardiac muscle with a mild infiltrate, principally macrophages, which peaked on day 15. T lymphocytes were also maximal on day 15 (12% of the infiltrate). Rejected grafts from untreated recipients showed accumulation of IFN-gamma mRNA but low levels of IL-10, TGF-beta, and IL-13. In hearts rejected by treated recipients, IFN-gamma mRNA did not increase and TGF-beta mRNA was higher. In LTS, IL-10, TGF-beta, and IL-13 transcripts were up-regulated (P<0.001), while IFN-gamma mRNA decreased (P<0.001). In both groups, IL-4 expression remained at a nonsignificant level. CONCLUSIONS: The profile of cytokine mRNAs in LTS could result in part from CsA, known to up-regulate TGF-beta and to down-regulate IFN-gamma. Moreover, CsA does not inhibit IL-10 production by monocyte/macrophages, the major infiltrating cells (60%). Lastly, LTS is induced in the absence of IL-4, which suggests that the high IL-4 production could simply be correlated with LTS without being a condition for it.

Animals↗
PubMed1997

[Tricalcium phosphate, vector of antibiotics: gentamycin and vancomycin. In vitro physicochemical characterization, study of biomaterial porosity and gentamycin and vancomycin elution].

We have investigated a Vancomycin and Gentamycin loaded macroporous tri-calcium phosphate-type beta-ceramic, Calciresorbr. Elution kinetics of Vancomycin and Gentamycin from spheric implants was studied by varying porosity and initial concentrations; then, the other following parameters, that can be modulated and are likely to be involved in this elution process, were analysed: Antibiotic charge: quantitative analysis (titration). qualitative analysis by scanning electron microscopy. Material's porosity: qualitative analysis: optical and scanning electron microscopy. quantitative analysis by stereology and treatment. This physicochemical characterization would favour correct manufacturing of new macroporous synthetic bioceramics in order to achieve satisfactory elution kinetics and homogenous materials.

Biocompatible Materials↗
PubMed1975

Essay of any ventilators by means of a pulmonary model with adjustable resistance, compliance and vital capacity.

After a critical study of classic lung models, showing that linear resistances are not faithful nor justified and that pneumotachograph is not a good measuring apparatus because of its inaccuracy (it changes calibration according to the nature of gas mixture and needs integration to determine volumes), authors present their own lung "model". In this model, it is possible to adjust resistance, compliance, vital capacity and residual volume. Parabolic resistances are used, because they more approach physiologic ones. Building of resistances (diaphragms), compliances (rigid tanks with adjustable elements), vital capacity (elastic membrane between two grills) is simple to realise and easy to reproduce. Measures of pressure and volume are given directly by gauges and are insensitive to gas nature, which is important in respiratory physiology. Flow-rates are deducted from volume values. The lung model can be used in a twin-cell shape to show the effects of artificial ventilation in case of pulmonary asymmetry. Examples given underline the interest of having a model with resistances easy to build and an adjustable vital capacity.

Airway Resistance↗