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M P Defresne

Publications and source records attributed to M P Defresne.

At least 55 records · Page 3Linked to original sources
PubMed1990

Effect of interferon-gamma and tumor necrosis factor-alpha on lymphoepithelial interactions within thymic nurse cells.

Isolated thymic nurse cells (TNC) represent a specialized microenvironment in vivo where thymocytes interact specifically with subcapsular epithelial cells. They are thought to play a critical role in the process of T cell differentiation. We demonstrate that recombinant murine interferon-gamma and recombinant human tumor necrosis factor-alpha can act on these interactions: they stimulate TNC-derived epithelial cells to establish interactions with thymocytes in vitro and to form new lymphoepithelial complexes. This phenomenon is partially inhibited by anti-Ia monoclonal antibodies. Implications of these findings for normal intrathymic differentiation are discussed.

Animals↗
PubMed1990

Cellular events in radiation-induced lymphomagenesis.

Fractionated whole-body irradiation induces thymic lymphomas in most of treated C57Bl/Ka mice. The cellular events occurring during the latency period consist of the emergence of preleukaemic cells and of marked alterations to the T-cell lineage and the microenvironment within the thymus. The proportions of the various thymocyte subsets are modified, suggesting a blockage in the normal differentiation process. Thymic epithelial cells are functionally modified, leading to decreased interactions with immature thymocytes. Interestingly, bone marrow grafting early after irradiation, which inhibits the development of lymphomas, induces the disappearance of preleukaemic cells from the thymus, whereas thymocyte subpopulations and thymic epithelium are restored. Interferon gamma and tumor necrosis factor alpha also prevent the onset of lymphomas. Studies on the effect of bone marrow transplantation and cytokine inoculation in split-dose irradiated mice should allow characterization of the factors that modulate the progression of preleukaemic cells towards the neoplastic state.

Animals↗
PubMed1990

Abnormal thymocyte subpopulations in split dose irradiated C57BL/Ka mice before the onset of lymphomas. Effects of bone marrow grafting.

Fractionated whole-body X irradiation (4 x 1.75 Gy at weekly intervals) induces a high percentage of thymic lymphomas in C57BL/Ka mice. The present work reports the phenotypic alterations of thymocyte subpopulations during the preleukemic period: there were a decrease of CD4+ CD8+ cells and an increase of CD4- CD8- and CD4- CD8+ cells. Marrow grafting early after irradiation that prevents lymphoma development restores the thymocyte subpopulations. In many instances, transplantation of 'preleukemic thymocyte inoculate' gives rise to an active and long lasting repopulation of recipient thymuses. However in all cases, donor lymphomas can develop after inoculation of 'preleukemic thymocyte inoculate'.

Animals↗
PubMed1989

N-acyl dehydroalanines protect from radiation toxicity and inhibit radiation carcinogenesis in mice.

N-Acyl dehydroalanines have shown free radical scavenging activity. They react with and scavenge mainly oxygen-derived free radicals such as the superoxide anion (O2-.) and the hydroxyl radical (HO.). Ortho-methoxyphenylacetyl dehydroalanine (AD-20) protects total-body irradiated mice against the toxicity induced by X-rays when delivered as a single dose of 700 rads in a short period of time. This degree of protection was of the same order of magnitude as that obtained with the aminothiol S-2-(3-aminopropylamino)-ethylphosphorothioic acid (WR-2721). The radioprotection of AD-20 is extended to all other doses of X-rays tested (from 600 to 800 rads). Furthermore, AD-20 inhibits the development of thymic lymphomas in C57Bl/Ka mice undergoing a leukaemogenic course of irradiation (4 x 175 rads applied at weekly intervals). We postulate that AD-20 may act as a radioprotector and anticarcinogenic agent, most probably by inactivating the oxygen-derived free radicals formed during water radiolysis.

Alanine↗
PubMed1989

Neuroendocrinology of the thymus.

The neuropeptides oxytocin (OT) and vasopressin (VP) are synthesized in the human thymus in a similar way as in the hypothalamo-neurophypophyseal system. Immunocytochemistry with polyclonal and monoclonal antibodies revealed that immunoreactive OT- and VP-producing cells are localized in the subcapsular cortex and medulla of human and murine thymuses. The epithelial nature of the neuroendocrine thymic cells is demonstrated by their immunostaining with a monoclonal antibody against cytokeratin. An original example of a neuroendocrine-immune microenvironment is given by the thymic nurse cells which are composed of a large neuroendocrine epithelial cell enclosing numerous mitotic immature thymocytes. These observations and the previously reported mitogenic and immunomodulatory properties of VP and OT upon mature T cells and thymocytes strongly support the existence of a neuroendocrine thymo-lymphoid axis and an active role of thymic VP and OT in T cell differentiation and activation.

Humans↗
PubMed1989

Tumor necrosis factor and interferon gamma inhibit the development of radiation-induced thymic lymphomas in C57BL/Ka mice.

Recombinant tumor necrosis factor and/or gamma-interferon were injected into C57BL/Ka mice after completion of a whole body split dose irradiation, which usually induces thymic lymphomas in more than 90% of the animals. The survival and the incidence of thymic lymphomas were significantly reduced in the cytokine-injected irradiated mice. The protective effect was similar to that obtained by grafting normal bone marrow cells after irradiation. The mechanisms of lymphoma inhibition by TNF or IFN-gamma are discussed.

Animals↗
PubMed1989

Control of lymphoepithelial interactions within thymic nurse cells by gamma-interferon and tumor necrosis factor alpha. Possible role in the modulation of intrathymic education?

The role of cytokines in the process of intrathymic differentiation is not yet clearly established. The results presented in this paper demonstrate that interferon-gamma and tumor necrosis factor-alpha regulate 'in vivo' and 'in vitro' the interactions between epithelial cells and thymocytes within thymic nurse cells. The mechanism of action of these cytokines and their possible physiologic role 'in vivo' are discussed.

Animals↗
PubMed1989

Radiation leukemia virus: a marker for the study of intrathymic T cell differentiation.

Radiation Leukemia Virus (RadLV) is a retrovirus, which displays a highly specific thymotropism; after inoculation into young C57 BL/Ka mice, active virus replication is observed only in thymocytes and thymic lymphomas develop in most treated mice. The specific interaction between RadLV and the thymus resides in the particular susceptibility to infection of the most immature cells involved in the intrathymic lymphoid differentiation pathway and of non lymphoid thymic stromal cells. Recent data obtained from 'in situ' hybridization studies for detection of viral transcripts yield more detailed informations on these intriguing interactions.

Animals↗
PubMed1989

Further studies on the mechanism of radiation induced thymic lymphoma prevention by bone marrow transplantation in C57BL mice.

Whole body fractionated irradiation induces thymic lymphomas in C57BL/Ka mice after a latent period during which intrathymic lymphopoiesis is modified; thymocyte numbers are subnormal and the epithelial component of thymic nurse cells (TNCs) is altered as estimated by the number of TNCs in vivo and by its ability to interact with immature thymocytes in vitro. A graft of normal bone marrow cells immediately after the last irradiation prevents the development of lymphomas; but when such a graft is performed 1 month later, it does not inhibit the emergence of tumors. In both cases the grafted precursors home and repopulate the thymus. However, the delayed graft does not exert any effect upon the altered epithelial component of TNCs, whereas the early one restores the numbers of TNCs and the function of their epithelial component. The results thus demonstrate that lymphoid thymic repopulation by a bone marrow graft is not sufficient to prevent the development of lymphomas and that there is an intimate relationship between tumor development and alterations of nurse cells microenvironment.

Animals↗
PubMed1988

The neurohormonal thymic microenvironment: immunocytochemical evidence that thymic nurse cells are neuroendocrine cells.

Thymic neuroendocrine cells were identified by immunofluorescence in the murine thymus through the use of monoclonal antibody A2B5, and specific polyclonal antisera against neurophysin (NP), oxytocin (OT) and arginine vasopressin (AVP). Two reactive regions were clearly identified: the subcapsular cortex and the medulla. A close correspondence was observed between A2B5-reactive and NP-immunoreactive cells in the medulla. An important epithelial population of the subcapsular cortex, the thymic nurse cells (TNCs), were found to be A2B5-positive and to contain immunoreactive NP, OT and AVP. The neuroendocrine nature of TNCs was further substantiated by their high reactivity with an antiserum against neuron-specific enolase. These observations demonstrate the presence in the thymus gland of an original neuroendocrine microenvironment which could be of functional importance in the mediation of central influences upon T lymphocyte differentiation.

Animals↗
PubMed1988

Enzyme analysis of thymic nurse cells.

Thymic nurse cells (TNC) were characterized according to their enzyme content. The following enzymes: Lactate dehydrogenase (LDH) isoenzymes, adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) were evaluated. When the enzyme profile of the TNC were compared with the one found in the different thymocyte subpopulations, the ADA/PNP ratio was very low and similar to the early thymocytes, whereas the LDH isoenzymes approached the pattern of the cortical thymocytes. This enzyme profile suggests that the enzyme content of the TNC is dependent on the presence of at least two different thymocyte subpopulations, the early thymocytes and the cortical thymocytes.

Adenosine Deaminase↗
PubMed1987

[Interaction of radiation-induced preleukemia cells and bone marrow grafts in C57BL/Ka mice].

The repopulation of thymus inoculated with radiation-induced preleukemia cells was studied in 400 R irradiated mice grafted with normal bone marrow cells. These marrow cells gave rise to an actively regenerating thymic progeny, as well as in 400 R treated mice receiving only a bone marrow graft. Moreover, the marrow graft did not prevent the progression of inoculated preleukemic cells towards lymphoma growth.

Animals↗