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Biomedical subjects

G Gras

Publications and source records attributed to G Gras.

At least 37 records · Page 2Linked to original sources
PubMed1996

CD40/CD40L interactions and cytokines regulate HIV replication in B cells in vitro.

Using our in vitro model of normal B cell infection, we investigated whether cellular interactions and/or cytokines directing the B cell response also regulate HIV replication. Phorbol esters and CD40 Ab plus IL4, added prior to infection, substantially increased subsequent viral replication. Postinfection, IL2 with or without IL4 and, to a lesser extent, CD40/CD40L interactions enhanced viral replication. In contrast, IL10 down-regulated HIV replication induced by cytokines, without affecting spontaneous or CD40 Ab-induced replication. Both enhancing and inhibitory effects of cytokines on viral replication were independent of their ability to modulate B cell proliferation. Thus, these two phenomena seem to be independently regulated in human B cells.

Animals↗
PubMed1996

Mechanisms of opsonized HIV entry in normal B lymphocytes.

Using our in vitro model of normal B cell infection that functions with low doses of HIV but requires virus opsonization by seropositive patient serum, and complement, we analyzed what receptors allowed virus entry. Here, we show that HIV infection of B cells occurs through 2 major receptors: the CD4 antigen and the CR1/CR2 complex. These 2 pathways work independently since a complete inhibition of virus entry requires both CD4 and CD21/CD35 blockade on CD4dim tonsillar B cells whereas only the latter is critical on CD4-negative B cells.

Antibodies, Monoclonal↗
PubMed1996

Anti-HIV potential of a new interferon, interferon-tau (trophoblastin).

Antiretroviral effects of a new class of interferon (IFN), IFN-tau, were compared with those of IFN-alpha in primary peripheral blood lymphocytes (PBLs) and monocyte-derived macrophages (MDMs), infected in vitro by human immunodeficiency viruses type 1, HIV-1/LAI, and HIV-1/DAS isolates, respectively. Cells were treated with recombinant IFN 24 h before or after HIV infection and then continuously exposed. Viral replication was monitored twice a week by quantifying the reverse transcriptase activity in cell culture supernatants. Integrated proviral DNA was monitored 24 h after infection in IFN-tau-pretreated MDMs, using specific gag gene amplification by the polymerase chain reaction. IFN-tau inhibited HIV-1 replication in both PBLs and MDMs as well as in peripheral blood mononuclear cells (PBMCs). IFN-tau was 35-fold more potent than IFN-alpha in PBLs and 100-fold more potent in MDMs. Differences were observed in the amount of integrated proviral DNA between untreated and 10 IU/ml IFN-tau-treated HIV-infected MDMs. IFN-tau exhibits significant anti-HIV activity in comparison to IFN-alpha, and like other IFNs, it seems to interact with several steps of HIV replication cycle.

Antiviral Agents↗
PubMed1996

Cytokine response of B lymphocytes from splenic lymphoma with villous lymphocytes: correlation with TNF-RII (p75) and CD11c expression.

We studied the immunophenotype and the functional reactivity to cytokines of blood cells from eight patients with Splenic Lymphoma with Villous Lymphocytes (SLVL). Cells from all cases exhibited moderate to high levels of membrane immunoglobulin, CD22 and CD40 antigens and light chain restriction (kappa/lambda: 1.7/1). CD44, CD54 and CD11b expression was detected in all cases whereas CD11c was expressed in only four cases (50%). CD11c+ cells lacked CD21 and CD23 expression whereas CD11c cells expressed both these antigens. Cells from most patients (7/8) responded to IL2 whereas only four responded to IL4 and three to TNF alpha. The response to TNF alpha correlated with spontaneous TNF-RII and CD11c expression. Although two days of culture induced the TNF-RII expression in CD11c cells, they remained unresponsive to TNF alpha. These two groups of SLVL patients also differed by IL10 mRNA content: the former (CD11c+, TNF-RII+) contained TNF alpha and IL10 mRNA whereas the latter (CD11c, TNF-RII) lacked IL10 mRNA, even after two days of culture. There were thus two groups of SLVL patients: CD11c+ and CD11c, exhibiting different patterns of cytokine response and production. These groups may correspond to different cell origins or different progression stages of the disease.

Aged↗
PubMed1995

Clearance of HIV infection in 12 perinatally infected children: clinical, virological and immunological data.

OBJECTIVE: A case of HIV infection clearance in a perinatally infected infant has been recently reported. We report here on the molecular, biological and clinical features of such virus clearance in 12 children. DESIGN AND METHODS: We performed a retrospective analysis of the diagnosis in our 6-year cohort of 188 children born to HIV-seropositive mothers. HIV-1 was detected by coculture of infant peripheral blood mononuclear cells (PBMC) with cord blood cells, direct culture of infant cells, and DNA polymerase chain reaction (PCR). The children were diagnosed three times during the first 3 months of life and then followed up over a postnatal period of 18-36 months. RESULTS: The 12 reverted children had at least two positive PCR in at least two amplified regions. Among them, six were tested positive in culture/coculture assay, and five were treated long-term with zidovudine. Thus, seven out of 12 reversions cannot be attributed to antiretroviral therapy. All the virological results became negative during the first year of life, and serology lowered to negative values between 9 and 23 months. We could not find any correlation between either neutralizing or antibody-dependent cellular cytotoxicity-mediating antibodies and HIV clearance. CONCLUSION: In our cohort, we showed that an unexpected number of children born to HIV-seropositive mothers (6.7%) cleared HIV infection during the first year of life, and subsequently became seronegative. Interestingly, most of these children exhibited unspecified clinical signs during the first months of life. Five of these children were tested positive only by PCR, which suggests a low virus load and could, at least partly, explain spontaneous clearance. However, 4 years later, among the seven remaining infants, two seronegative children presented recurrent hepatosplenomegaly, which may indicate the presence of hidden virus not detectable by peripheral blood testing.

CD4-CD8 Ratio↗
PubMed1994

Induction of humoral and cellular immunity to simian immunodeficiency virus: what are the requirements for protection?

In an effort to produce a strong humoral and cellular immune response that might protect against simian immunodeficiency virus (SIV) infection, groups of five rhesus macaques each were immunized intramuscularly at 0, 2 and 6 months with 100 micrograms of an inactivated preparation of SIV/Delta B670 in either an oil-in-water emulsion with Ribi Detox, containing mycobacterial cell wall skeleton and monophosphoryl lipid A (CWS/MPL) (group A) or a water-in-oil emulsion with incomplete Freund's adjuvant, containing CWS/MPL for the first two injections (group B). Animals were challenged with 10-100 monkey ID50 of monkey-cell-grown SIVmac251 3 months after the last injection, along with a group of four unvaccinated controls. Group B animals demonstrated the strongest immune responses following immunization, including neutralizing antibody titres against the challenge virus ranging from 160 to 320 and SIV-specific ELISA titres ranging from 10(5)-10(6) on the day of challenge, as well as strong in vitro lymphoproliferative and interleukin-2 (IL-2) production responses to the immunogen. Neutralizing antibody was not detectable in group A animals, ELISA titres were lower (10(2)-10(4)), no in vitro lymphoproliferative responses were observed, and in vitro IL-2 production was less pronounced. No protection against challenge was observed in either group. Moreover, group B animals exhibited a more pronounced clinical response following challenge than either group A animals or controls, consisting of hyperthermia and a greater degree of lymphadenopathy on day 7, followed by hypothermia and generally higher levels of serum viraemia on day 14.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Antibody-dependent cellular cytotoxicity and neutralization of human immunodeficiency virus type 1 by high affinity cross-linking of gp41 to human macrophage Fc IgG receptor using bispecific antibody.

Human monocytes/macrophages, which express Fc receptors for IgG are involved in human immunodeficiency virus type 1 (HIV-1) infection and pathogenesis. These receptors are known to mediate numerous immunological functions including cell-mediated killing and possibly targeting of HIV to the lysophagosome monocyte-derived macrophage (MDM) entry route for virus neutralization. To study both activities in HIV-1 infection, MDM Fc gamma RI was specifically selected using bispecific antibody (Bs-Ab) containing whole human monoclonal antibody against gp41 and the Fab' fragment of murine anti-Fc gamma RI 22.2 antibody. Bs-Ab was found to mediate potent antibody-dependent cellular cytotoxicity and virus neutralization.

Antibodies, Bispecific↗
PubMed1993

Complement and virus-specific antibody-dependent infection of normal B lymphocytes by human immunodeficiency virus type 1.

We tested the susceptibility of human purified, normal B lymphocytes to human immunodeficiency virus type 1 (HIV-1) infection, in the presence or absence of complement-sufficient serum and of virus-specific antibodies. Virus replication was detected when cells were infected in the presence of both complement and anti-HIV antibodies (C'-ADE conditions), by day 2 postinfection. Similar results were obtained when B lymphocytes were purified either from peripheral blood (three healthy donors) or from tonsils (four individuals with chronic tonsillitis). HIV infection was shown by polymerase chain reaction (PCR) detection of proviral sequences (gag and pol genes), by p24 antigen synthesis, and by cocultivation assay with MT2 cells. The higher p24 production was obtained when B cells were preactivated for 2 days by phorbol 12-myristate 13-acetate (PMA) before infection and then cultured in the presence of low-molecular weight B-cell growth factor (LMW-BCGF). Expression of virus envelope glycoprotein (gp) 120 could also be detected on a subpopulation of B cells (CD19+, CD22+) by flow cytometry. Blocking experiments with monoclonal antibodies (MoAbs) against CD4, CD21 (complement receptor 2 [CR2]), CD35 (CR1), CD19, and CD5 surface molecules indicated that infection of B cells involves CD4, CD21, and CD35 antigens. Indeed, blocking of CD4 receptor inhibited 10% of p24 production, and blocking of both CD21 and CD35 led to extinction of p24 signal. CR-dependent pathway is thus a major route for C'-ADE of HIV infection in normal B cells. Our results emphasize the importance of studying interactions between HIV and the complement system for better understanding infection mechanisms and the major dysfunctions of B cells in HIV-infected individuals.

B-Lymphocytes↗
PubMed1993

In vitro infection of human macrophages with human T-cell leukemia virus type 1.

The tropism of the human T-cell leukemia virus type 1 (HTLV-1) for the cells of monocyte-macrophage lineage was evaluated by the coculture of blood monocyte-derived macrophages, with irradiated cells of HTLV-1 producing cell lines MT2 or C91/PL. The susceptibility to HTLV-1 was assessed by the detection of viral DNA using the polymerase chain reaction method. HTLV-1 gene expression in the cells was detected using in situ hybridization and by immunofluorescent staining of viral antigen. The presence of type C virus-like particles detected by electron microscopy and the ability to infect normal cord blood lymphocytes demonstrated that the infected macrophages produced infectious virus. These results indicate that human macrophages are susceptible in vitro to productive HTLV-1 infection, and thus might be involved in the pathogenesis of HTLV-1-related diseases.

Cells, Cultured↗
PubMed1993

[Role of neutralizing antibodies in protection of the fetal from an HIV positive mother].

The goal of this study is to compare serum Titers of Neutralizing antibodies in HIV 1 infected mothers to the virological status of their newborns. 38 infant-mothers couples were tested. Serum Neutralizing antibodies Titers of the mothers were tested the day of birth. Virological status of new borns was determined by peripheric blood mononuclear cells culture and PCR. 18 Newborns were HIV 1 infected. In 9 cases mothers had no neutralizing antibodies: 7 newborns were HIV 1 infected. In 4 cases mothers had high level of neutralizing antibodies (< 640): none of the newborns was infected. In 25 cases mothers had intermediate value of neutralizing antibodies (between 80 and 320): 11 newborns were HIV 1 infected. Women with neutralizing antibodies to HIV 1, were less likely to transmit HIV 1 to their infants than pregnant women without neutralizing antibodies. Serum neutralizing antibodies titers of pregnant women might be of predictive value in vertical transmission of HIV 1. Further investigations are needed.

Acquired Immunodeficiency Syndrome↗
PubMed1983

[Effect of temephos on acetylcholinesterase activity in the brain of Tilapia guineensis. 3: Comparative effect of temephos and 3 substitute insecticides].

The Onchocerciasis Control Programme (OCP) is realized in the major part of the treated area by weekly applications of temephos in biotopes of simulles larvae. This insecticide is very effective and its impact on the aquatic fauna is evaluated by means of periodic samplings of the fauna. Therefore, the most sensitive way of tracking down fish poisoning is by studying the brain acetylcholinesterase depression. Evaluated on Tilapia guineensis this lowering is moderate when operational doses are used by OCP. The discovery of resistence to temephos incited researchers of OCP to try remplacement insecticides. Among these, chlorphoxim, chlorpyrifos-methyl and pirimiphos-methyl proved to be the most effect of these three organophosphorus compounds to that of temephos on the acetylcholinesterasic activity of the brain of Tilapia but using a much higher dosage (0,05 mg/l during 24 hrs that is 144 times more than for temephos). The results demonstrate that the three remplacement insecticides have on inhibitive effect plainly more important than that of temephos and that the retour to normal activity requires a much longer time.

Acetylcholinesterase↗
PubMed1982

[Effect of temephos on the acetylcholinesterase activity of the brain of Tilapia guineensis. 1: Experimental study at operative doses].

After having exposed during 10 minutes the Tilapia guineensis to a concentration of 0,05 mg/l of temephos (concentration of a larvicide used for the field test), the authors note a lowering of the acetylcholinesterastic activity of the brain to an order of 25%. The return to a normal activity is achieved within 20 to 25 days. A new exposure, happening one week after the first, provokes a further lowering before the return to a normal value. The authors question themselves on the consequences of these chemical attacks repeated on a weekly basis during antilarval treatments in the struggle against the onchocercose.

Acetylcholinesterase↗