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E Joly

Publications and source records attributed to E Joly.

53 records · Page 3Linked to original sources
PubMed1992

Neuronal cells are deficient in loading peptides onto MHC class I molecules.

Virally infected neurons avoid destruction by cytotoxic T lymphocytes (CTLs) by failing to express major histocompatibility complex (MHC) class I molecules. Like neurons in vivo and in primary culture, the OBL21 neuronal cell line expressed barely detectable levels of MHC class I molecules. This correlated with very low levels of mRNAs for the MHC class I heavy chains (alpha C). OBL21 cells also fail to provide MHC class I molecules with the peptides necessary for their efficient assembly and transport to the cell surface. This function can be restored by treatment with interferon-gamma (IFN-gamma). The mRNA for peptide transporters HAM1 and HAM2 was not detectable in OBL21 neuronal cells, but was induced by IFN-gamma treatment. Hence, the ability of neurons to evade CTL-mediated killing results from expression at low levels of the MHC class I alpha C, the peptide transporters HAM1 and HAM2, and possibly other genes of the peptide-loading machinery.

Animals↗
PubMed1992

Presence of a novel nuclear lamina protein in Raji cells.

In mammalian tissues, the nuclear lamina is composed of the major lamins A, B, and C, and minor lamins D/E. Although lamin B is present in all cell types, lamins A and C are absent from embryonic cells and most undifferentiated cells from hematopoietic lineage. We have investigated the nuclear lamina protein composition of the Raji cell line, lymphoblast-like cells established from a Burkitt lymphoma patient. Lamins A and C were confirmed absent by immunodetection and Northern blot analysis. Besides lamins B and D/E, a protein migrating around 71 kilodaltons was recognized by a serum directed against the nuclear lamina of BHK-21 fibroblasts. Cellular localization by sequential extraction established this 71-kilodalton protein as an exclusive component of the nuclear lamina fraction. These results indicate that the nuclear lamina has a more complex composition than previously thought to be the case for cells devoid of lamins A and C.

Animals↗
PubMed1991

Viral persistence in neurons explained by lack of major histocompatibility class I expression.

Viruses frequently persist in neurons, suggesting that these cells can evade immune surveillance. In a mouse model, 5 x 10(6) cytotoxic T lymphocytes (CTLs), specific for lymphocytic choriomeningitis virus (LCMV), did not lyse infected neurons or cause immunopathologic injury. In contrast, intracerebral injection of less than 10(3) CTL caused disease and death when viral antigens were expressed on leptomeningeal and choroid plexus cells of the nervous system. The neuronal cell line OBL21 expresses little or no major histocompatibility (MHC) class I surface glycoproteins and when infected with LCMV, resisted lysis by virus-specific CTLs. Expression of MHC heavy chain messenger RNA was limited, but beta 2-microglobulin messenger RNA and protein was made normally. OBL21 cells were made sensitive to CTL lysis by transfection with a fusion gene encoding another MHC class I molecule. Hence, neuronal cells probably evade immune surveillance by failing to express MHC class I molecules.

Acute Disease↗
PubMed1991

Persistent infection with lymphocytic choriomeningitis virus enhances expression of MHC class I glycoprotein on cultured mouse brain endothelial cells.

Brain endothelial cells (EC) represent a major component of the blood/brain barrier, which activated CTL cross to enter the central nervous system. Several viruses also penetrate the central nervous system through the blood stream via the brain EC. The studies reported here focus on understanding the principles and consequences of interactions among viruses, lymphocytes, and EC in the brain. As shown persistent but not acute infection by lymphocytic choriomeningitis virus enhances the expression of MHC class I glycoproteins on the brain EC of mice. This increase in MHC expression during viral infection does not seem to result from the release of cytokines. However, replicative virus is required, because UV inactivated virus fails to enhance MHC expression. Viral determinants appear on EC surfaces after infection and serve as targets for CTL directed lysis. In contrast, neurons (OBL 21 neuronal cell line), which express negligible amounts of MHC class I glycoproteins, show no gain in MHC markers during persistent viral infection and are not targets for virus-specific CTL killing.

Animals↗
PubMed1991

Generation of a functional cDNA encoding the LdH2 class-I molecule by using a single-LTR retroviral shuttle vector.

The use of a new single long-terminal-repeat retroviral shuttle vector has allowed us to obtain copies of the Ld gene with the first seven exons spliced correctly, as well as many other partially spliced or aberrantly recombined copies. Nucleotide sequencing performed on double-stranded DNA with primers specific for the vector and for the coding region of the gene, allowed rapid screening of the recovered plasmids. Synthetic oligodeoxyribonucleotides were then used to link the 5 nt of the last exon, and the functionality of the cDNA copy was verified by expression in transfected L(TK-) cells. Cells that produced the Ld antigen were detected by immunofluorescence and were shown to synthesize an immunoprecipitable molecule of the expected size. In addition, Ld-producing cells were susceptible to killing by Ld-restricted cytotoxic T-lymphocytes. This material should prove useful for mutagenesis and for expression in cell types in which expression of the genes of the major histocompatibility complex appears to be highly regulated.

Amino Acid Sequence↗
PubMed1990

Vaccination and protection from a lethal viral infection: identification, incorporation, and use of a cytotoxic T lymphocyte glycoprotein epitope.

The outcome of infection by lymphocytic choriomeningitis virus (LCMV) is determined largely by the cytotoxic T lymphocyte (CTL) response of the host. In H-2b mice, the anti-glycoprotein (GP) response is directed to at least two epitopes, one located at GP aa 272-286 and a second in GP-1. Here we show that the second epitope can be minimally identified by amino acid residues GP 34-40 (AVYNFAT). The epitope is restricted by the Db class I glycoprotein. Characterization of these CTL epitopes allowed us to address the role(s) played by each epitope when expressed singly in the control of a lethal challenge with LCMV. Here we show that a single immunization with a recombinant vaccinia virus (VV) vaccine expressing LCMV GP aa 1-59 confers protection to H-2b mice from lethal LCMV infection. In contrast, a VV expressing LCMV GP aa 272-293, although recognized by CTL, does not protect. We show that the success or failure of protective immunization is determined by the ability of the immunizing sequences to prime for CTL in vivo. Although the GP 278-286 epitope when contained as a "minigene" fails to induce CTL, when incorporated in the normal GP "backbone" it successfully elicits CTL. These observations suggest that the "minimal" recognition sequence alone may not be sufficient to induce a protective CTL response in vivo. Thus a single CTL epitope can protect against a lethal virus infection, but to achieve an effective vaccine, the immunizing sequences must be carefully selected.

Amino Acid Sequence↗
PubMed1990

[Two-years' experience of ambulatory anesthesia in otorhinolaryngology in children].

Three hundred children were anaesthetized for E.N.T. operations. The anaesthetic consultation took place one week prior to operation. The anaesthetic comprises premedication, inhalation of halothane for infants, or propofol drip for the others with tracheal tubing for 10% of them. Recovery in every case is supervised in the recovery room. There are few setbacks with this method. Eleven children were not accepted for operation for sociological or medical reasons (Willebrand diseases) and only 3 had to remain in hospital until the following day due to slow recovery from anaesthetic.

Adenoidectomy↗
PubMed1989

Molecular analyses of a five-amino-acid cytotoxic T-lymphocyte (CTL) epitope: an immunodominant region which induces nonreciprocal CTL cross-reactivity.

The cytotoxic T-lymphocyte (CTL) response to lymphocytic choriomeningitis virus infection determines the outcome of infection. Here we show that this response in BALB/c mice (H-2d), when analyzed both at the primary CTL level and using CTL clones, is predominantly monospecific. The vast majority of CTL have a common specificity for a single epitope in the virus nucleoprotein, which can be minimally identified by amino acids GVYMG. This epitope is presented by the Ld class I glycoprotein. We used these data to design a subunit CTL vaccine, whose effectiveness is demonstrated in the accompanying report (L. S. Klavinskis, J. L. Whitton, and M. B. A. Oldstone, J. Virol. 63:4311-4316, 1989). Further analysis indicates that, while CTL clones share a common minimal epitope, they differ in their ability to recognize cells infected with a related but distinct strain of lymphocytic choriomeningitis virus. Studies on the molecular nature of CTL cross-reactivity indicate that CTL induced by similar sequences may cross-react in a unidirectional manner. These novel observations suggest that CTL vaccines, to achieve optimal effectiveness, should not simply include virus sequences which will yield a CTL response; the immunizing sequences should also be selected to ensure that the fine specificities of the induced CTL are such that they maximize the chance of recognizing serotypically diverse strains.

Amino Acid Sequence↗
PubMed1989

Polymorphism of cytotoxic T-lymphocyte clones that recognize a defined nine-amino-acid immunodominant domain of lymphocytic choriomeningitis virus glycoprotein.

To assess the heterogeneity of cytotoxic T lymphocytes (CTLs) directed against viral epitopes, we studied six class I major histocompatibility complex-restricted (H-2Db) CTL clones that recognize the same 9-amino-acid immunodominant epitope, amino acids 278 to 286 from envelope glycoprotein 2 (GP2) of lymphocytic choriomeningitis virus (LCMV). Using Southern blot analysis of beta-chain rearrangements, we found that each clone has a unique restriction pattern, providing evidence of the independent derivation of the clones and suggesting that the clones express different beta-chain sequences for their T-cell receptor. All these clones killed syngeneic target cells infected with strain Armstrong or WE of LCMV; however, two of the six clones failed to recognize target cells infected with the Pasteur strain of LCMV. Sequence analysis of LCMV Armstrong, WE, and Pasteur GP in the region of amino acids 272 to 293 demonstrated a single-amino-acid substitution at amino acid 278 in the region of the defined epitope in the Pasteur strain. Interestingly, one of the two CTL clones that failed to lyse LCMV Pasteur-infected target cells nevertheless efficiently and specifically killed uninfected target cells coated with the appropriate LCMV Pasteur peptide, while the other clone failed to do so. This indicated a dichotomy between processing of the synthesized protein initiated by infection and a peptide exogenously applied. Dose-response studies utilizing several peptides with substitutions in GP amino acid 278 indicate that CTL recognition occurs at the level of a single amino acid and suggest that this difference is likely recognized at the level of the T-cell receptor.

Amino Acid Sequence↗
PubMed1981

Growth regulation of two rat adenocarcinoma cell lines by dexamethasone and progesterone.

We have studied the effect of steroids on cell proliferation in two continuous cell lines derived from rat mammary tumors induced by 7, 12-dimethyl-benz (a) anthracene (DMBA) and N-nitrosomethylurea (NMU). These cell lines contain high concentrations of glucocorticoid and androgen receptors but no estrogen and progesterone receptors as previously shown (1). The cell proliferation was evaluated by measuring [3H] thymidine incorporation into DNA, cell number, and DNA content. Dexamethasone was found to markedly stimulate cell proliferation in a dose-dependent manner, suggesting that it was acting via the glucocorticoid receptor. The effect of 5 alpha-dihydrotestosterone (DHT) was weaker since a stimulation of [3H] thymidine incorporation was contrasted by the absence of a constant increase of cell proliferation. Progesterone partially stimulated NMU cell growth and totally inhibited the stimulatory effect of dexamethasone in both cell lines. The synthetic progestin R5020 displayed a similar activity to that of progesterone. These results show that progestins can directly modulate the growth of mammary cancer cells even in the absence of progesterone receptor by interacting on the glucocorticoid receptor. We conclude that progestins act mostly as partial agonist-antagonists of glucocorticoids in these two rat mammary adenocarcinoma cell lines.

Adenocarcinoma↗
PubMed1977

Increased plasma adrenaline concentrations in benign essential hypertension.

Plasma adrenaline, noradrenaline, and dopamine concentrations and plasma renin activity were measured in the supine position and after standing for 10 minutes in 14 patients with sustained benign essential hypertension and in five patients with labile hypertension. Results were compared with values obtained in 11 normotensive control subjects. In controls plasma noradrenaline concentrations increased with age, while plasma adrenaline values tended to decrease with age. No significant difference in mean plasma noradrenaline was found between hypertensive and control subjects, but plasma noradrenaline seemed slightly increased in a proportion of hypertensive patients aged less than 50. Plasma adrenaline was considerably raised in both supine and standing positions in eight patients with sustained hypertension and in two with labile hypertension. Dopamine concentrations and plasma renin activity were similar in all groups studied. The finding of significantly raised plasma adrenaline concentrations in a large proportion of hypertensive patients supports the hypothesis that the activity of the sympathetic nervous system is increased in essential hypertension. Measurement of plasma adrenaline seems to be a more sensitive index of this activity than that of plasma noradrenaline.

Adult↗