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E J Jenkinson

Publications and source records attributed to E J Jenkinson.

At least 73 records · Page 4Linked to original sources
PubMed1989

The effects of anti-CD2 antibodies on the differentiation of mouse thymocytes.

Using a rat monoclonal antibody against mouse CD2, we determined the expression of this marker on thymocytes during ontogeny. CD2 expression becomes detectable at day 15 and reaches adult levels (approximately 95% positivity) by day 19. Furthermore, the effect of anti-CD2 antibodies on T cell differentiation was analyzed by addition of antibodies to thymus organ cultures or repeated injection into newborn mice. Anti-CD2 antibodies inhibit CD2 expression in organ cultures and drastically reduce its expression on thymocytes and peripheral lymphocytes in vivo. In either situation, suppression of CD2 expression does not significantly alter the generation of T cells expressing CD3, CD4, CD8 and T cell receptor V beta 8. These results do not support a role for CD2 in early steps of thymocyte differentiation.

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PubMed1989

Antigen-induced apoptosis in developing T cells: a mechanism for negative selection of the T cell receptor repertoire.

Herein we have investigated the ability of antigen to induce thymocyte death by apoptosis on the basis that this may be the mechanism for the deletion of autoreactive cells during T cell development. We show that the ability of the bacterial "superantigen" staphylococcal enterotoxin B to cause specific depletion of V beta 8+ cells when added to thymus organ cultures is accompanied by DNA degradation into oligonucleosomal fragments, indicating that depletion involves apoptosis. Our results provide the first direct evidence that antigen-induced apoptosis can be triggered in developing T cells.

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PubMed1989

Developmental control of lymphokine gene expression in fetal thymocytes during T-cell ontogeny.

We have used the technique of in situ hybridization to investigate the expression of lymphokine genes by immature thymocytes during intrathymic development. In 13-day fetal thymocytes a population of cells constitutively produces low levels of interleukin 2 (IL-2) and interleukin 4 (IL-4) mRNAs. A second phase of lymphokine gene expression occurs in the majority of 15-day thymocytes, and a population of cells constitutively produces both IL-2 and IL-4 mRNAs. Thymocytes at 14 days of gestation and after 16 days up until birth do not express detectable lymphokine mRNA. By contrast, the population of IL-2 receptor mRNA-producing thymocytes increases progressively up to 15 days of gestation, and expression thereafter decreases up to birth. In addition, thymocytes expressing interferon gamma mRNA were not present until just prior to birth. Our findings indicate developmental control of lymphokine and lymphokine receptor gene expression in fetal thymocytes during ontogeny.

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PubMed1989

Regulatory factors in lymphoid development.

The process of T lymphocyte maturation within the thymus involves a complex series of differentiation events involving T cell receptor gene rearrangement and expression. A beginning has now been made at defining the growth and differentiation signals required for these events. An additional level of complexity is provided by the selection of the repertoire of T cell specificities so that the pool of peripheral T cells available for interaction with antigens is 'shaped' by the thymus. The maturation of stem cells to B lymphocytes takes place in association with bone marrow stromal cells. Large numbers of newly-formed B cells can now be generated in vitro on stromal cell layers. Stromal cells capable of supporting B lymphopoiesis have now been cloned and, recently, a growth factor (IL-7) which acts on early B cells has been identified.

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PubMed1988

Murine CD2 gene expression during fetal thymus ontogeny.

The expression of the murine CD2 gene and the interleukin 2 receptor IL2R has been investigated during fetal thymus ontogeny. CD2 mRNA was undetectable at embryonic day 14 but was readily detectable at day 15 of gestation. Surface IL2R expression was maximal at day 14 and was clearly detectable at day 13. These results indicate that IL2R expression precedes that of CD2 by at least 2 days.

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PubMed1988

Factors affecting the acceptance of deoxyguanosine-treated thymus allografts.

dGuo-treated mouse embryo thymus lobes depleted of lymphoid and dendritic cells are not rejected by normal allogeneic mice despite expression of class I and class II major histocompatibility (MHC) antigens on thymic epithelial cells. Our results suggest that host mice are not tolerant to donor antigens, but treated lobes survive because thymic epithelial cells are not immunogenic. Multiple grafts of dGuo-treated lobes are rejected perhaps because numbers of residual dendritic cells reach a threshold necessary for priming. Mice previously primed by injection of spleen cells reject dGuo-treated thymus lobes, and crossreactions between major and minor histocompatibility antigens can be demonstrated. The acceptance of dGuo-treated thymus allografts by normal mice provides a system for investigating the requirements for priming.

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PubMed1988

The effects of anti-CD3 antibodies on the development of T-cell receptor alpha beta + lymphocytes in embryonic thymus organ cultures.

Cells expressing the gamma delta T-cell receptor in association with CD3 molecules appear in the embryonic thymus before alpha beta CD3+ cells. We have added anti-CD3 antibodies to organ cultures of mouse thymus removed from embryos before any CD3+ cells have appeared, with the aim of blocking the function of the latter as they are generated in the cultures. Our results show that these antibodies affect the maturation of precursors of alpha beta + cells so that D-J but not V-D-J beta-chain arrangements predominate. In contrast, full length alpha gene transcripts are produced. These results are compatible with the view that the early population of gamma delta CD3+ cells plays a role in the maturation of the alpha beta + population.

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PubMed1988

Proliferation of thymocytes in relation to T-cell receptor beta-chain expression.

During proliferation and differentiation of maturing thymocytes, T-cell receptor beta-chain products are first expressed in the cytoplasm. Only subsequently are they expressed on the cell surface, presumably as part of the alpha beta/CD3 receptor complex. This study uses double immunofluorescence labelling to identify these cytoplasmic and surface phases separately in relationship to cell-cycle parameters. The use of a mitotic arrest agent and tritiated thymidine autoradiography both show that cells with cytoplasmic beta-chains are in cell cycle, whereas cells with surface beta-chains are cycling slowly, if at all.

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PubMed1987

Survival of deoxyguanosine-treated fetal thymus allografts is prevented by priming with dendritic cells.

Allogeneic thymus lobes rendered alymphoid by treatment with deoxyguanosine are not rejected in normal mice despite expression of class I and class II MHC antigens on donor cells. The results presented here show that the injection of as few as 10,000 cells from dendritic cell-enriched populations is followed by the rejection of deoxyguanosine-treated grafts. These findings support the notion that treated thymus grafts do not provoke rejection because they lack dendritic cells, which are destroyed by deoxyguanosine.

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PubMed1987

T-cell immunity to murine Moloney sarcoma virus-induced tumours: L3T4+ T cells are necessary for resistance to primary sarcoma growth, but Lyt-2+ T cells are required for resistance to secondary tumour cell challenge.

Experimental protocols have been devised to deliniate the importance of T-cell subsets in immunity to Moloney sarcoma virus-induced tumours using the surface antigens L3T4 and Lyt-2 as markers of helper and cytotoxic cells, respectively. Because the monoclonal antibodies used have been shown to deplete T-cell subsets in vivo, we have been able to study the role of L3T4+ and Lyt-2+ T cells in the primary response to MSV for the first time. The results clearly show that L3T4+ T cells are the most important in resistance to the viral challenge. Mice injected with monoclonal antibodies to L3T4 grew large tumours following injection of a viral innoculum that was resisted by untreated mice or mice injected with monoclonal antibodies to Lyt-2. The same monoclonal antibodies were used to remove primed L3T4+ or Lyt-2+ T cells in vitro in adoptive transfer experiments. Normal unirradiated mice were protected from a challenge of WR19L lymphoma cells when they were given primed spleen and lymph node cells intraperitoneally. Depletion of Lyt-2+ T cells before adoptive transfer abolished this protective effect. Depletion of L3T4+ cells had no effect on the ability of primed cells to transfer immunity. Thus, while L3T4+ T cells are required for the primary rejection of MSV, only primed Lyt-2+ T cells are able to transfer resistance to a secondary challenge of lymphoma cells.

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PubMed1986

An investigation of T cell receptor gene rearrangement and expression in organ cultures of normal embryonic thymus and Thy-1+ cells of nude mice.

We have shown that beginning with 14-day mouse embryo thymus, rearrangements of T cell receptor beta-chain genes and transcripts of alpha and beta chains culminating in the generation of T cell receptor-bearing cells can be obtained in organ cultures. We have failed to detect rearranged beta chain genes, and beta chain transcripts or membrane receptors in concanavalin A-activated nude spleen cells, although we cannot exclude the possibility that a minor subpopulation of nude Thy-1+ cells may express T cell receptors. Our results suggest that the thymus is both necessary and sufficient for generation of T cell receptor-bearing cells and that organ culture provides a system for further investigation of the mechanisms involved.

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PubMed1986

Generation of cells expressing cytoplasmic and/or surface T-cell receptor beta chains during the development of mouse fetal thymus.

We have used a double immunofluorescence technique to identify newly formed cells expressing cytoplasmic and/or surface T-cell receptor beta chains in mouse embryo thymus. In addition, we have localized these cells to the developing thymic cortex by immunoperoxidase labelling of frozen sections. The first positive cells appear in small numbers in the thymus at Day 15 of gestation and express cytoplasmic but not surface beta chains (C beta+). At Day 16 of gestation, cells appear that express small capped areas of surface beta chains as well as cytoplasmic beta chains (C beta+S beta+ cells). Just prior to birth, a cohort of cells appears that express surface beta chains but no cytoplasmic beta chains detectable by the methods employed (S beta+ cells). These results and vincristine mitosis-blocking studies suggest that a proliferating population of cortical thymocytes accumulate cytoplasmic beta chains before giving rise to T cells that express surface beta chains (presumably in association with alpha chains). When a monoclonal antibody to beta chains is present in organ cultures of embryonic thymus, C beta+ thymocytes continue to be generated but there is an absence of S beta+ cells. The latter appear after the cultures are transferred to fresh medium not containing the antibody.

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PubMed1985

Stromal cell types in the developing thymus of the normal and nude mouse embryo.

The anatomical distribution of various nonlymphoid cell types in the embryonic mouse thymus in vivo and in vitro, as well as in the thymic rudiment of the nude mouse embryo, has been studied. For this purpose a panel of monoclonal antibodies, ER-TR3, 4, 5, 6 and 7, directed to various types of stromal cells of the mouse thymus, was used in combination with immunoperoxidase labeling on frozen sections. It was shown that as early as day 13 in thymic ontogeny distinction of TR4+ cortical epithelial cells and TR5+ medullary epithelial cells is possible. Thus, as far as stromal components are concerned, the thymus at day 13 in ontogeny is already subdivided into cortex and medulla. At day 13, Ia (TR3) was expressed in a focal pattern in the medulla subsequently appearing throughout both cortex and medulla by day 16. The thymic rudiment of the nude mouse embryo differs markedly from the normal embryonic thymus in its lack of demonstrable Ia antigen. Furthermore, TR4 and TR5 were only expressed on occasional epithelial cells lining the cysts of the nude thymus in a mutually exclusive fashion. The majority of stromal cells of the nude thymus, however, is negative for all ER-TR antibodies tested. In addition, we have shown that in organ cultures the organization of the stroma of thymic lobes remains intact, at least for a period of 11 days. Embryonic thymi cultured in the presence of deoxyguanosine, which causes depletion of lymphoid cells, also contain cortical and medullary areas as identified by the presence of TR3,4+ and TR5+ stromal cells. This indicates that the lack of organization in the nude thymus is not simply due to the absence of lymphoid cells.

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