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E J Jenkinson

Publications and source records attributed to E J Jenkinson.

At least 91 records · Page 5Linked to original sources
PubMed1984

Early events in T lymphocyte genesis in the fetal thymus.

There is considerable uncertainty about the nature and level of maturation of the stem cells which colonize the thymus. Arguments are presented here which raise doubts about the claims that these cells have undergone substantial maturation along the T-lineage pathway prior to migration to the thymus. Instead, emphasis is placed on the role of thymic stromal cells in T-lymphocyte maturation. The heterogeneous nature of these cells is well established, but progress is described in analyzing the various cell types and their embryological origins. In particular, the expression of the major histocompatibility complex (MHC) antigens on thymic stromal cells might be relevant to the understanding of restriction and tolerance. The early phases of thymus lymphocyte differentiation are described; but no clear account of the generation of T-cell subsets from immature cells can, as yet, be offered.

Animals↗
PubMed1984

Characterization of stromal cell populations in the developing thymus of normal and nude mice.

The role of the thymic stromal components in T cell maturation has been investigated by compairing stromal composition in the developing thymus of normal mice with that of nude mice which are unable to support thymopoiesis. Stromal cell populations have been characterized using monoclonal antibody recognizing class II (Ia) major histocompatibility complex antigens, monoclonal antibody A2B5 recognizing GQ gangliosides characteristic of neuroendocrine cells and monoclonal antibody LE.61 recognizing a determinant associated with the tonofilaments of simple epithelia. Using these probes we have shown that the majority population of Ia+, LE.61+ cells is distinct from the A2B5+ stromal population and that both these populations appear early in normal thymus development showing a similar pattern in vivo and in thymus lobes developing in organ culture. In the nude thymic rudiment both Ia and LE.61 labeling are absent supporting previous conclusions on the epithelial nature of the thymic defect in these animals. In contrast, A2B5+ cells are present in the nude thymic rudiment indicating that these cells are unlikely to share the same developmental origin as the Ia+ epithelial population. In functional terms these results suggest that the Ia+ LE.61+ components, deficient in the nude mouse, are essential for normal thymus function and that whatever the function of the A2B5+ population, alone they are not sufficient to support thymocyte development.

Animals↗
PubMed1982

Development of cytolytic T lymphocyte precursors in organ-cultured mouse embryonic thymus rudiments.

The appearance of immunologically competent cells in the organ-cultured mouse fetal thymic rudiment has been investigated. Fetal thymuses removed at 14 d of gestation and cultured for 7-21 d were assayed for their content of cytolytic T lymphocyte precursors (CTL-P) directed against H-2d alloantigens. Whereas CTL-P were undetectable within fetal thymus until 18-19 d of gestation, their frequency in the organ-cultured fetal thymus was similar to, or greater than that found in the normal adult thymus. This direct demonstration of the appearance of alloreactive CTL-P in a closed in vitro system should provide an accessible model for the investigation of interactions between developing T cells and the thymic microenvironment.

Animals↗
PubMed1982

Detection of Thy-1, T-200, Lyt-1 and Lyt-2-bearing cells in the developing lymphoid organs of the mouse embryo in vivo and in vitro.

The appearance of cell membrane antigens on lymphoid cells of the embryonic thymus in vivo and in vitro using monoclonal antibodies in immunoperoxidase tests on frozen sections and in two-color immunofluorescence tests on cells suspensions was studied. It was shown that cells are heterogeneous with respect to Lyt antigen expression from the earliest stages of ontogeny. Thus, after 16 days gestation, some cells are Lyt-1+2-, others are Lyt-1-2+ and some are Lyt-1+2+. However, for various reasons which are discussed, we hesitate to suggest that this finding demonstrates independent derivation of the various T cell subsets. In the absence of cell migration, organ cultures of embryonic thymus generate enriched populations of Lyt-1+2- and Lyt-1-2+ cells, i.e. cells with functional "mature" phenotypes. It was not found that cells bearing T cell antigens are generated in organ cultures of fetal liver and spleen. This result argues against the thymus-independent generation of T cells in these organs.

Animals↗
PubMed1982

Effect of deoxyguanosine on lymphopoiesis in the developing thymus rudiment in vitro: application in the production of chimeric thymus rudiments.

On the basis of reports that deoxyguanosine is selectively toxic for adult T lymphocytes, the usefulness of this compound in the production of lymphocyte-depleted embryonic thymus rudiments in an in vitro organ culture system was investigated. The results showed that a period of exposure to deoxyguanosine causes depletion of the lymphoid cells while the stromal elements continue to survive, with many of the cells showing an epithelial morphology and expression of I region products of the major histocompatibility complex (MHC). When associated with either fetal liver or another thymus fragment as a source of T cell precursors in transfilter experiments, these "empty" thymuses become recolonized, enabling the production of chimeric thymus with stromal and lymphoid cells of different haplotypes. In combination with functional assays, this system offers an entirely in vitro approach to questions relating to the repertoire potential of T cell precursors from different sources and the role of the thymus in tolerance and MHC restriction.

Animals↗
PubMed1981

Major histocompatibility complex antigen expression on the epithelium of the developing thymus in normal and nude mice.

The expression and distribution of antigens coded by the K and I regions of the major histocompatibility complex in the developing thymus of normal and nude mice has been investigated using monoclonal antibodies. Both immunohistological studies of intact rudiments and in vitro labeling of cultures derived from microdissected rudiments indicate that, while K region antigens are present on epithelial and mesenchymal elements, I region antigens are only detectable on the epithelium. This view is also substantiated by the selective absence of I region antigens in the abnormal nude thymic rudiment where the defect is considered to be epithelial in nature. The findings are considered in relation to the role of the thymus in providing an environment for the differentiation and selection of developing T cells, and it is proposed that the Ia-expressing epithelial elements play a central role in these functions.

Animals↗
PubMed1981

Expression and function of major histocompatibiliby complex antigens in the developing thymus: studies on normal and nude mice.

Direct access of lymphoid precursors to the thymic environment appears to be an essential step in the differentiation of normal T cell populations and it is possible that intimate cellular interactions between T cells and the thymic stroma are involved in selective processes leading to self-tolerance and major histocompatibility complex (MHC) restriction. As an approach to investigating the intrathymic environment, MHC antigen expression during normal thymic development and lymphopoiesis, and in the embryonic thymus of T cell-deficient nude mice, has been examined. Evidence has been obtained to show that MHC antigens controlled by both the K and I regions are expressed from an early stage on epithelial cells in normal thymus development but that the thymic rudiment in nude mice shows a selective absence of I regions antigens. The implications of these findings for T cell development and the derivation and constitution of the intrathymic environment are considered.

Animals↗
PubMed1980

Lymphocyte differentiation and major histocompatibility complex antigen expression in the embryonic thymus.

During embryogenesis, stem cells migrate from the bloodstream into the thymic rudiment where they proliferate and differentiate into T lymphocytes. The epithelial cells of the thymic stroma may influence these processes by providing hormonal and/or contact stimuli to the developing lymphoblasts. Recently, it has been shown that T cells 'learn' to recognise the major histocompatability complex (MHC) antigens during thymic lymphopoiesis and become MHC-restricted. Their subsequent response to other antigens can only occur in the context of MHC antigens of the haplotype encountered in the thymus. Little is known, however, of antigen expression on the thymic stroma which may provide the reference framework on which this MHC restriction is based. In this study we use monoclonal antibodies to show that antigens of the K and I regions of the MHC are detectable on cells of the embryonic mouse thymic stroma from around the 14th day of gestation, just when lymphocyte differentiation is commencing. Furthermore, I-region antigen (Ia antigen) expression is probably limited to thymic epithelium at this stage of gestation and we have not detected Ia on other epithelial tissues of the pharyngeal complex. This pattern of expression is consistent with a role for the thymic stroma in MHC restriction, perhaps by the selection of lymphoid cells for survival on the basis of their recognition of stromal MHC determinants.

Animals↗
PubMed1978

Major histocompatibility complex and non-major histocompatibility complex antigens on mouse ectoplacental cone and placental trophoblastic cells.

The expression of major histocompatibility complex and non-major histocompatibility complex antigens on mouse trophoblast cultured from two defined stages of development was investigated by the sensitive in vitro mixed haemadsorption assay. Outgrowths obtained 3 to 5 days after explanation of 7 1/2-day ectoplacental cones contained a mixed population of cells. Those with a giant cell morphology showed no haemadsorption with congenic H-2 antisera and were reactive with non H-2 antiserum only in the CBA strain. Other, smaller cells were reactive for both H-2 and non-H-2 in all strains examined except for C57BL, where the cells were nonreactive for H-2. Monolayer cultures of 13 to 14-day placental suspensions tested 24 hr after preparation were strongly reactive for both H-2 and non-H-2. The identity and alloantigenic status of the cells are discussed in relation to their function in maternal-foetal immunological interactions.

Animals↗
PubMed1978

Localization of trophoblast-defined surface antigens during early mouse embryogenesis.

The binding pattern of a rabbit antiserum raised against mouse-ectoplacental-cone trophoblast on component cell populations in the pre-implantation and early post-implantation mouse embryo has been examined at the electron-microscope level using an immunoperoxidase-labelling technique. Binding was not detectable on the 1-cell stage, appeared at low levels at the 8-cell stage and was heavy on the trophectoderm and its trophoblast giant cell and extra-embryonic ectoderm descendants in the post-implantation embryo. In contrast, immunosurgically isolated 3 1/2-day inner cell masses (ICM) showed only slight labelling, whilst ICM derivatives in the 7 1/2-day embryo were unlabelled. The results indicate that the antiserum may be identifying a trophoblast-specific surface determinant(s), which appears with the differentiation of the trohectoderm and is maintained on some of the cell populations derived from this tissue at least until the early post-implantation stages.

Animals↗
PubMed1976

Detection of alloantigens during preimplantation development and early trophoblast differentiation in the mouse by immunoperoxidase labeling.

An immunoperoxidase-labeling technique allowing visualization of antibody binding to the cell surface at the electron microscopical level has been employed an an analysis of H-2 and non-H-2 alloantigen expression on the early mouse embryo. The presence of non-H-2 antigenic determinants has been confirmed on eight-cell, morula, and blastocyst stages of development. Contrary to previous reports, however, low levels of H-2 antigen have also been detected on the blastocyst. This is the earliest stage at which H-2 has been shown to be expressed on the fertilized mouse egg and may reflect the greater resolution of the immunoperoxidase technique. Using two different models to study the critical peri-implantation stages, those of experimentally induced blastocyst activation and blastocyst outgrowth in vitro, it has been demonstrated that antigen loss occurs on the trophectoderm at the time of implantation, and that this is not necessarily dependent upon maternal influence. It is suggested that the loss may be an important factor in the prevention of maternal immune rejection during the establishment of the fetal allograft. The two major components of the early postimplantation conceptus display a striking differential in antigenic status. The embryonic sac shows a high degree of peroxidase labeling, while the ectoplacental cone trophoblast is unlabeled. These findings add support to the concept of antigenic neutrality of the early trophoblast and its role in the maintenance of a normal fetomaternal immunological equilibrium.

Animals↗
PubMed1976

Detection of receptors for immunoglobulin on human placenta by EA rosette formation.

Direct evidence for the existence of Fc receptors on the surface of first trimester and term human placental cells has been obtained by the use of an antibody-coated red cell (EA) rosette assay. The modification of a Ficoll density gradient separation procedure for placental cell population in conjunction with dye uptake experiments, cytocentrifuge preparations and cytological analysis has enabled an identification of the rosette-forming cells in the mature placenta as predominantly, if not entirely, syncytiotrophoblastic. The significance of these findings, together with those demonstrating the presence of cell-surface Fc receptors on the chorionic membrane, are considered in relation to the transmission of immunoglobulin from mother to foetus and to the protection of the foetus as an intra-uterine allograft.

Cell Membrane↗