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L Tentori

Publications and source records attributed to L Tentori.

At least 37 records · Page 2Linked to original sources
PubMed1992

Induction of apoptosis in thymocytes by prostaglandin E2 in vivo.

In vivo administration in mice of a synthetic analog of prostaglandin E2 (PGE2) caused a selective and dramatic decrease of CD4+CD8+ double-positive, CD3/T-cell-receptor-alpha beta(lo) cells in the thymus. This loss was corticosteroid-independent and not affected by Cyclosporin A. The disappearance of CD4+CD8+ thymocytes was strictly correlated with the induction of apoptosis inside the thymus as shown by morphological studies and by the induction of intracellular transglutaminase expression. Considering that PGE2 has been found to be produced by different cell populations inside the thymus, these results indicate that PGE2 may act as endogenous signals for apoptosis during T-cell differentiation.

16,16-Dimethylprostaglandin E2↗
PubMed1990

IL-2 reverses the inhibition of cytotoxic T-cell responses induced by 5-(3,3' dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) in vitro.

One of the major limitations in the use of triazene compounds for inducing increased immunogenicity of tumor cells in vivo (i.e. chemical xenogenization) is the profound immunodepressive activity of these drugs. The present study analysed the inhibitory effects of DTIC on various T-dependent immune responses in mice in an attempt to determine the mechanism of action and appropriate treatments for reverting the immune damage produced by the agent. Results obtained show that treatment with DTIC in vivo produced: (a) inhibition of spleen cell proliferation; (b) reduced IL-2 production in response to allogeneic stimuli; (c) reduction of the generation of IL-2R + CD8 + cells in allogeneic MLC; (d) inhibition of allo-CTL generation. The addition of IL-2 to MLC on day 2 of the co-culture restored full allogeneic CTL responses. These data suggest that exogenous IL-2 could be used to counteract DTIC-induced depression of T-cell reactivity, which is presumably involved in hosts' responses against autochthonous xenogenized tumor cells.

Animals↗
PubMed1990

Are the IL-2 receptors expressed in the murine fetal thymus functional?

It is well established that the majority of murine fetal thymocytes (day 15 of gestation) express receptors for interleukin 2 (IL-2), but the functional significance of these IL-2 receptors (IL-2Rs) is not clear. In situ hybridization data show a developmentally regulated expression of IL-2 and IL-2R mRNA. IL-2 binding studies were performed on fetal thymocytes and the results show the presence of both high (kD approximately equal to 20 pM) and low (kD approximately equal to 10 nM) affinity IL-2Rs. These IL-2Rs are indeed functional: intact fetal thymic lobes (but not cell suspensions) cultured in IL-2 exhibited an in vitro proliferative response at 20 pM of IL-2, corresponding with the presence of a functional high-affinity IL-2R on fetal thymocytes. The IL-2-dependent growth was primarily observed in the IL-2R+ thymic subset, which contains the CD3-/CD4-/CD8- precursor thymocytes. Furthermore, in vitro blocking of IL-2 in intact fetal thymic lobes resulted in a reduction in the cell yield, which predominantly affected the expansion of the immature CD3-/CD4-/CD8- thymocytes. Our findings strongly support the concept that the IL-2/IL-2R pathway is responsible for the proliferation of precursor cells within the fetal thymus.

Animals↗
PubMed1989

A novel gamma delta T cell receptor for antigen adds limited diversity to the gamma delta repertoire in adult thymus.

The surface expression of CD3-associated TCR chains on hybridoma cell lines derived from adult gamma delta thymocytes was analyzed. These cell lines were unusual, in that a) they expressed a surface heterodimer consisting of a 40- and a 42-kDa chain, i.e., comprised of chains different from any previously reported gamma delta-TCR all of which express C gamma 1- or C gamma 2-encoded gamma-chains; b) their CD3-associated TCR could not be categorized as alpha beta-TCR dimers, despite the similarities in m.w. of the TCR chains, because full size 1.3-kb beta-chain mRNA capable of encoding a functional beta-chain could not be detected in these cells; c) neither of the receptor chains could be precipitated with anti-C gamma 1C gamma 2-peptide antisera. Biochemical analysis demonstrated that the 42-kDa delta-chain is a novel chain, which differs from any reported delta-chains in size, charge and number of glycosylation sites. Collectively, the data on analysis of the 40-kDa chain strongly suggest that it represents a gamma-chain encoded for by the C gamma 4 locus, protein products of which have not yet been reported in the thymus. This gamma-chain was also unique, in that its isoelectric point was much lower than that of other gamma-chains. The gamma- and delta-chains on these C gamma 4-expressing hybridomas were indistinguishable from one another in size and charge (as determined by nonequivalent pH gradient electrophoresis/SDS-PAGE analysis and analysis after endoglycosidase treatment). Because the cell lines were randomly chosen from large panels of hybridomas, these results may well imply strikingly nonrandom pairing of thymocyte-derived C gamma 4 chains and the delta-chains reported here. Thus, only limited additional gamma delta repertoire diversity may be generated by availability of this gamma delta-TCR in the thymus.

Aging↗
PubMed1988

Essential role of the interleukin 2-interleukin 2 receptor pathway in thymocyte maturation in vivo.

The role of the IL-2-IL-2-R pathway in thymocyte differentiation in vivo is unknown. We have examined fetal thymocyte development in vivo, under conditions where all IL-2-R were saturated from day 13 of gestation with anti-IL-2-R mAbs that were previously shown to render mature T cells unable to respond to IL-2. This produced a dramatic change in the composition of developing T cells: thymocytes from day 1 neonatal mice born to anti-IL-2-R-treated mothers did not contain CD4+ or CD8+ single-positive cell populations. In addition, no generation of surface TCR beta chain-expressing T cells or antigen-reactive functional T cells occurred in treated mice. These data suggest that IL-2-IL-2-R interactions provide signals crucial to in vivo intrathymic development of mature T cells.

Animals↗
PubMed1988

Differentiation of Ia-reactive CD8+ murine T cells does not require Ia engagement. Implications for the role of CD4 and CD8 accessory molecules in T cell differentiation.

The present study was undertaken to assess the Ia differentiation requirements of CD8+ class II-allospecific CTL, whose CD8+ phenotype is apparently "discordant" with their MHC class II reactivity. To do so, we compared the effect of in vivo anti-Ia blockade on the differentiation of Ia-reactive CD8+ CTL with its effect on the differentiation of CD4+ T cells. We found that anti-Ia blockade did not detectably interfere with the differentiation of CD8+ Ia-reactive CTL, even though it arrested the differentiation of CD4+ T cells. Thus, the differentiation of CD4+ T cells is strictly dependent upon Ia engagement, whereas the differentiation of CD8+ T cells, even those with reactivity against MHC class II alloantigens, does not require Ia engagement. These results support the concept that Ia-reactive CD8+ T cells are conventional CD8+ CTL, probably selected by self-class I MHC molecules during differentiation, whose receptors fortuitously crossreact on MHC class II alloantigens. Taken together, the present data indicate an intimate relationship between CD4/CD8 expression with MHC class specificity during T cell differentiation and selection. We suggest that an active triggering role for CD4 and CD8 accessory molecules in T cell differentiation is best able to explain these observations.

Animals↗
PubMed1988

Proliferation and production of IL-2 and B cell stimulatory factor 1/IL-4 in early fetal thymocytes by activation through Thy-1 and CD3.

To examine which cell surface molecules can operate as transducers of activation signals to early fetal thymocytes, we analyzed the ability of mAb to CD3 and Thy-1 to induce fetal thymocyte activation. Both proliferation and lymphokine secretion were used as measures of activation. We show that anti-CD3 antibodies induce activation of fetal thymocytes as early as day 13 of fetal thymus development, 2 days before CD3 can be detected by flow cytometry. In addition, an alternative activation signal can be delivered to fetal thymocytes through the Thy-1 molecule as early as it is expressed, i.e., day 13. Both CD3- and Thy-1-mediated activation of day 15 fetal thymocytes results in expansion of cells expressing a CD3-gamma delta receptor complex; no CD3-alpha beta receptor complex could be detected. IL-2 production induced by CD3- and Thy-1-induced activation of fetal thymocytes is evident at the 13th day of gestation. Finally, an additional lymphokine B cell stimulatory factor-1 (BSF-1)/IL-4 (so far known only to be produced by mature CD3- cells), is also produced by fetal thymocytes. The results demonstrate that at least two cell surface molecules, Thy-1 and CD3, can function as pathways of activation in fetal thymocytes, and that at least two lymphokines, IL-2 and BSF-1/IL-4, are produced upon activation. These findings may well reflect a role for the early appearance of CD3- cells in thymus ontogeny.

Animals↗
PubMed1988

Comparative studies between in vitro and in vivo effects of human beta-interferon on natural killer activity and its relevance to immunochemotherapy.

A good correlation was found between in vivo and in vitro responses of peripheral MNC from breast cancer patients and the NK boosting effect of human beta IFN. In vitro immunochemistry studies showed that marked antitumor effects were obtained against cultured cancer cells when a widely used chemotherapeutic agent such as 5-FU was combined with nonsensitized spontaneously cytolytic MNC, preactivated in vitro with beta IFN. These results suggest that the in vitro susceptibility assay of MNC to IFNs could be used for predicting favorable responses to immunochemotherapy regimens employing IFNs as immunomodulating agents.

Cytotoxicity, Immunologic↗
PubMed1988

Limb lengthening in achondroplasia by Ilizarov's method.

In achondroplasts limb lengthening can restore the normal proportion of the body. The Ilizarov method of limb lengthening has been used in 37 patients, 23 of whom have had an adequate follow-up after operation. In this technique the cortex of the bone is partially cut, leaving the medulla intact; the two bone segments are then subjected to distraction by means of a special apparatus. The bone tissue between the two segments starts regenerating and this allows a considerable increase in length. The results and complications are reported. It is considered that this method is based on sound principles and is free of major risks.

Achondroplasia↗
PubMed1987

Influence of low-dose beta-interferon on natural killer cell activity in breast cancer patients subjected to chemotherapy.

The present study was designed to test whether immunomodulating doses of human beta-interferon would affect the natural cell-mediated cytotoxic function in untreated breast cancer patients or in those subjected to antitumor therapy. Analyses were performed on 11 breast cancer patients, 3 at stage 1 and 8 at stage 2, the latter being subjected to cyclophosphamide, methotrexate, 5-Fluorouracil (CMF) adjuvant chemotherapy. Five patients treated with CMF and 3 patients not subjected to adjuvant chemotherapy, received human beta-interferon (IF, 2 X 10(6) IU/patient, i.m.), on days 0,7, and 15 for 6 cycles of 31 days each. The natural killer (NK) activity (NKA) of peripheral blood mononuclear cells (MNC) was tested 24 and 48 h after low-dose IF administration. The results of NKA determinations carried out for the 6 cycles of treatment show that (1) chemotherapy alone depressed NKA; (2) IF alone increased NKA in stage 1 patients not treated with CMF; (3) IF antagonized the depressive activity of CMF on NK function and significantly augumented NKA in the case of low "basal" cytotocix activity detectable in MNC collected before IF administration. Parallel in vitro studies showed that the inhibitory effect on NKA provoked by CMF is due to cyclophosphamide present in the association and is effectively antagonized by IF. These data provide rational bases for using IF in immunochemotherapy regimens, when tumor cells are supposed to be susceptible to host control by the natural resistance function.

Adult↗
PubMed1986

A miniaturized cell-mediated cytotoxicity assay with human effector mononuclear cells.

A miniaturized method (Microtest, MIT) for detecting natural killer (NK) and antigen-elicited cell-mediated cytotoxicity has been developed. It retains the sensitivity and the efficiency of conventional macroassay (Macrotest, MAT). In comparison with the standard MAT, MIT provides a 5-fold reduction in the number of effector and target cells without changing the final reaction volume. This avoids the excessive relative evaporation that could occur in microassays employing limited reaction volumes. Moreover the use of V-bottom microtiter plates allows the recovery of 0.15 ml of supernatant, thus increasing the efficiency of 51Cr recovery. MIT was adopted for the evaluation of the NK activity of untreated or interferon (IFN)-treated human mononuclear cells (MNC) and for cold-inhibition and cytotoxic T-lymphocyte (CTL) assays. In the experiments performed with both macro and micro assays, comparable values of the percentage of specific lysis and of the number of lytic units were found. The slopes of the curves obtained with MIT are generally slightly lower than those detectable with MAT. The Pearson coefficient r2 is generally better for the macroassay although it can be considered acceptable in the microassay. The MIT described here appears to be a useful method, especially for providing information on natural resistance and cytotoxic T-lymphocyte systems in a number of pathological conditions characterized by a small recovery of effector cells from standard blood collection for analytical purposes.

Cell Line↗
PubMed1986

[Application of the Ilizarov technic in the lengthening of the humerus].

Lengthening of the humerus has been considered to be particularly risky because of the danger of neurological damage. The Ilizarov technique makes it possible to avoid complications. The authors have performed eight such lengthenings, with gains in length of 8 to 16 cms. Only one case was complicated by an ulnar and radial paralysis which recovered secondarily.

Achondroplasia↗
PubMed1985

Natural cell-mediated cytotoxicity: a micro assay suitable for clinical tests.

A micro version (microtest, MIT) of the 51Cr release assay for detecting Natural Killer activity (NK) has been developed. The test retains the sensitivity and the efficiency of conventional macroassay (macrotest, MAT) and provides a 5-fold reduction in the number of effector and target cells employed. In experiments performed with peripheral blood mononuclear cells (MNC), untreated or treated with interferon (IFN) or with hydrocortisone (Hy), comparable values of the percentage of specific lysis and of the number of lytic units were obtained using both MAT and MIT methods. Therefore MIT appears to be useful in monitoring the NK function of patients characterized by low MNC counts.

Animals↗
PubMed1985

[Treatment of septic or non-septic diaphyseal pseudoarthroses by Ilizarov's monofocal compression method].

The treatment of non-union of long bones is one of the best indications for the use of Ilizarov external fixation. The method is somewhat expensive but without risk. In 20 patients, use of the technique achieved healing in cases in which traditional methods such as bone grafts, plates or other types of external fixator had failed. The main advantages are avoidance of further vascular disturbance, a stable and elastic fixation and the possibility of early weight-bearing with consequent compression.

Adolescent↗
PubMed1984

Chemotherapy in hairy cell leukemia. Preliminary results of a nonaggressive regimen.

Three patients with hairy cell leukemia, only one splenectomized, were treated with a combination of vinblastine plus bleomycin at low doses. One achieved a complete remission and another achieved a good partial hematologic and bone marrow remission. Neither of them has relapsed after follow-up periods of 34 and 17 months, respectively. The third patient, although achieving a hematologic improvement, died because of a cytomegalovirus pneumonitis after 2 cycles of chemotherapy. Chemotherapy is not usually employed in the initial management of hairy cell leukemia. However, if life-threatening neutropenia and thrombocytopenia occur secondary to severe bone marrow leukemia infiltration and an improvement does not take place using alternative therapeutic strategies, chemotherapy should be taken into consideration. The nonaggressive chemotherapeutic regimen the authors propose induces a cytoreduction without an evident myelosuppression, and can be also employed on an outpatient basis.

Adult↗