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C Corbel

Publications and source records attributed to C Corbel.

At least 37 records · Page 2Linked to original sources
PubMed1996

Evidence for a thymus-dependent form of tolerance that is not based on elimination or anergy of reactive T cells.

The avian embryo has provided an appropriate model to study the ontogeny of the primary lymphoid organs, thymus and bursa of Fabricius. By using the quail-chick marker system the embryonic origin of the highly intricate cell components which form these organs could be traced back to the initial endodermal, mesodermal and ectodermal germ layers. The timing and dynamics of the incoming and outcoming flows of hemopoietic cells which characterize their lymphopoietic activity could be revealed in both quail and chick embryos. This knowledge served as a basis for an investigation on the role of the epithelial component of the thymus (derived from the pharyngeal endoderm) on tolerance to tissue graft and, by extension, tolerance to self. When this work was undertaken, the prevailing view was that exposure of the developing immune system to foreign antigens in the embryo allows them to be assimilated to self components in the mature animal. In fact, this was found to be true for allogeneic grafts between MHC-distinct chickens, of certain tissues, such as for instance wing tissues. However, in heterospecific transplantations, i.e. when a limb bud was grafted from quail to chick embryos, the chick host acutely rejected the foreign limb soon after birth. In contrast, grafts of the quail thymic epithelial (TE) rudiment resulted in the development of a chimeric thymus in which the foreign epithelial component was not only tolerated but able to induce full tolerance of the grafted wing from the same donor. By monitoring the amount of quail TE implanted we showed in addition that only part of the peripheral T-cell population had to differentiate in the context of the quail epithelial cells to induce tolerance to quail tissues. This pointed to the generation in the thymus of regulatory T cells, coexisting with specific anti-quail reactive T cells, but able to inhibit them from reacting against the quail wing antigenic determinants. A mammalian model was then devised to further study this mechanism of tolerance that we have qualified as "dominant" by opposition to the current model based on either clonal elimination or anergy which can be considered as recessive or passive. Nude mice of MHC type A were grafted with TE of E10 type B embryos. They became reconstituted for T-cell function but tolerant for B skin allografts. Spleen cells from such tolerant animals injected to naive A nude mice reconstituted T cell function in the recipient and transferred the tolerance to B skin grafts. Reducing the number of donor cells resulted in the segregation of the two phenomena. For low numbers the recipients were restored but not tolerant, thus showing the coexistence in the tolerant donor of anti-B reactive T cells together with regulatory cells able to abolish their reactivity against B determinants. Other experiments demonstrated that TE-induced tolerance does not rely on clonal deletion or anergy. This was shown on systems where elimination of cells directed toward superantigens was screened. It turned out that tolerance to skin grafts and superantigen T-cell deletion are unrelated phenomena. These observations strongly suggest that tolerance to self results at least in part from the interplay between cells potentially harmful for self component and others which exert a strong control on their reactivity. The latter cell type depends upon interactions of thymocytes with the endodermal component of the thymus.

Animals↗
PubMed1994

The major histocompatibility complex of chickens controls the infection of early chicken embryos by MC29 virus.

Embryos from isogeneic chicken lines belonging to different haplotypes and known to be resistant to infection by avian retroviruses of subgroups A and E were infected on the 3rd (E3) and 5th day (E5) of incubation with MC29 virus (MC29-RAV-1 pseudotype; A subgroup-derived envelope). Despite the trait for resistance, E3 embryos developed the specific heart tumors previously described in outbred E3 embryos. The CB line (B12/B12, C/AE) was more susceptible than the congenic line CC (B4/B4, C/AE). In both lines, the heart was the unique target at E3 for MC29. No tumors of the heart or other organs appeared upon infection at E5 or E10. In the A subgroup susceptible line 6 (B2/B2, C/E) both heart (50%) and skin (100%) were transformed upon E3 infection. Hybrids of line 6 with the CB line expressed skin (100%) and heart (95.4%) tumors. On the other hand, the 6 x CC combination revealed 96.7% of skin tumors while heart tumors occurred only in 1 of 31 embryos (3.2%). To distinguish the respective influences of the MHC and of the tv-a allele, crosses with the la line (B7/B7, C/O) were carried out and tested with MC29. The findings indicate that resistance of the embryos to MC29 heart tumors is associated with the B4/B4 haplotype, supporting the interpretation that the MHC has a role in MC29 cell tropism and v-myc expression. The target cells in tumors were determined by immunofluorescence staining. Cells infected in the heart belonged to the myogenic lineage, as expected from previous studies. In skin anomalies the epidermal cells were double-stained with anticytokeratin and anti-env antibodies, many cells in the dermis also reacted with anti env antibodies.

Alpharetrovirus↗
PubMed1994

Biochemical and functional characterization of an avian homolog of the integrin GPIIb-IIIa present on chicken thrombocytes.

We have analyzed the reactivity of a new mouse monoclonal antibody (mAb), 11C3, which identifies a cell marker detected on the surface of chicken thrombocytes. Tissue distribution studies have shown that only cells of the thrombocytic lineage in blood, spleen, and bone marrow are stained by 11C3. However, it does not react with other species such as quail, mouse, and man. The 11C3 mAb immunoprecipitates an heterodimeric molecule made of two bands with an apparent molecular weight of 112 and 90 kDa under nonreducing conditions and 112 and 26 kDa following reduction. This pattern of migration is similar to the one observed for members of the integrin family of cell adhesion molecules. We have used the previously described mAb AP-2, which is specific for the human platelet integrin GPIIb-IIIa and cross-reacts with chicken thrombocytes. We have shown that it immunoprecipitates two bands with an identical electrophoretic mobility. Cross-inhibition and immunodepletion studies reveal that the two antibodies recognize two different isoforms or two conformational variants of the same molecule. Moreover, our data demonstrate that in contrast with AP-2, 11C3 is a potent inducer of thrombocyte activation measured by cell aggregation, chemiluminescence, or release of [3H]serotonin. It also inhibits the adhesion of thrombin-activated thrombocytes to fibrinogen and, to a lesser degree, to fibronectin, in a dose-dependent manner. Altogether, these results indicate that this antibody identifies the avian homolog of the mammalian platelet integrin and fibrinogen receptor GPIIb-IIIa.

Animals↗
PubMed1994

A study of peripheral tolerance through embryonic grafts of the bursal epithelial rudiment between MHC-distinct chick embryos.

We report here that different organ grafts are not equally competent to induce tolerance of the host even if they are performed early in development, i.e. before the host's immune system has started to develop. We have grafted the epithelio-mesenchymal rudiment of the bursa of Fabricius between histoincompatible chicken embryos at E5 and found that the transplant is normally colonized by hemopoietic cells from the host and that a normal contingent of B cells is eventually produced. The grafted bursa is tolerated after birth for a few weeks (> or = 4-8) but is in all cases rejected by an immune mechanism which cannot be assimilated to the physiological involution process which occurs at 4-5 months of age. Moreover, even in the first month after birth, when the bursa is still healthy, skin grafts of the same MHC haplotype are promptly rejected. These observations are in contrast with the outcome of allogeneic limb bud grafts which are permanently tolerated after birth although in an unperfect manner. We show in addition that, as was the case in xenogeneic grafts of limb buds and bursas of Fabricius from quail and chick embryos, the allogeneic in situ graft to thymic epithelium of the MHC haplotype of the bursal implant induces tolerance of the bursa. One common point of xenogeneic and allogeneic embryonic grafts of limb bud, bursa and even thymic rudiments is that none of them induced a complete state of tolerance, since proliferation responses were always obtained in vitro in one-way host-donor mixed leucocyte cultures.

Animals↗
PubMed1993

The role of thymic epithelium in the establishment of transplantation tolerance.

From experimental observations on induction of transplantation tolerance, we discuss a model that accounts for tissue-specific tolerance to antigens not expressed inside the thymus. It is postulated that antigens presented to differentiating T cells by thymic epithelium (or at large within the thymic environment) positively select and activate self-reactive T cells. A developmental program and/or prevalent conditions in the thymic environment restrict the proliferative potential and the class of effector functions that can be exerted by differentiating T cells activated in the thymus. These do not mediate inflammatory or cytolytic activities, but instead will produce the appropriate mediators to inhibit aggressive effector activities by other T cells activated in their proximity. Such "regulatory" functions will be locally expressed at the periphery upon recognition of tissue antigens shared with the thymus, towards newly formed thymic emigrants directed at tissue-specific antigens expressed by the same "target" cells. This mechanism imposes "dominant tolerance", based on specific self-recognition and predominantly established in the embryonic and neonatal period. Throughout life, the process of thymic positive selection results in all newly-formed T cells being susceptible to such suppressive mechanisms, but becoming increasingly refractory with time in the resting, post-differentiative stage. Absence of antigen (nonself) in the embryonic and neonatal life therefore allows for the accumulation of such "suppression-resistant" antigen-reactive T cells that will mount aggressive responses upon antigenic exposure. Tolerance or immunity thus represent two classes of specific immune responses, the relative predominance of which is determined by the frequency of each type of effector T cell, representing the antigenic overlap between thymic and peripheral tissues, as well as the frequency of tissue-specific T-cell generation, and the kinetics of peripheral antigenic exposure. Tolerance induced by hemopoietic cells to all other tissues is also "dominant" and based on thymic colonization and persistence of antigenic cells, with the consequent positive selection of regulatory T cells and peripheral conditions for the establishment of suppression. Upon this simple model, that ensures "interclonal class regulation" by "bridging" regulatory and effector T cells through the recognition of different antigens on the same target cell, other mechanisms which are based on V-region interactions among T cells (Ben-Nun et al. 1981, Pereira et al. 1989, Webb & Sprent 1990, Gaur et al. 1993) might well operate to ensure "dominant tolerance" by self-reactivity and class regulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

BEN, a surface glycoprotein of the immunoglobulin superfamily, is expressed in a variety of developing systems.

We have previously identified a 95- to 100-kDa cell surface glycoprotein, which we named BEN (for bursal epithelium and neurons), that is widely expressed during chicken embryonic development. In the central nervous system, it is restricted to subsets of neurons including the motoneurons and the inferior olivary nucleus neurons (which provide the cerebellum with the climbing fibers) where its expression occurs during the phase of axonogenesis and synaptogenesis. In the present work, we show that BEN expression extends to a variety of tissues originating from the three embryonic germ layers. We have found that BEN immunopurified from neural, epithelial, and hemopoietic tissues is differently glycosylated and may or may not carry the HNK-1 epitope. We then cloned a full-length cDNA encoding this protein. Analysis of its sequence reveals that BEN is a member of the immunoglobulin superfamily. Two molecules with an identical cDNA sequence were recently reported: DM-GRASP [Burns, F. R., Von Kannen, S., Guy, L., Raper, J. A., Kamholz, J. & Chang, S. (1991) Neuron 7, 209-220] and SC1 [Tanaka, H., Matsui, T., Agata, A., Tomura, M., Kubota, I., Mcfarland, K. C., Kohr, B., Lee, A., Phillips, H. S. & Shelton, D. L. (1991) Neuron 7, 535-545]. Their pattern of expression and structural properties are consistent with those reported for BEN. Therefore BEN, DM-GRASP, and SC1 are likely to be the same molecule of the immunoglobulin superfamily.

Activated-Leukocyte Cell Adhesion Molecule↗