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Biomedical subjects

F Vuillier

Publications and source records attributed to F Vuillier.

16 recordsLinked to original sources
PubMed1992

Evidence for a viral superantigen in humans.

Superantigens bind class II major histocompatibility proteins and stimulate powerful proliferative responses of T lymphocytes bearing particular V beta sequences as part of their alpha beta antigen receptor. Exogenous bacterial superantigens are responsible for food poisoning and toxic shock syndrome. Murine virus-encoded self-superantigens induce clonal deletion of T lymphocytes. Although superantigen-like properties have been suggested for human immunodeficiency virus-1, no viral superantigen has been identified in humans. Here we report that the nucleocapsid of the rabies virus is an exogenous superantigen specific for V beta 8 human T lymphocytes which binds to HLA class II alpha-chains.

Antigen-Presenting Cells↗
PubMed1992

The bactericidal capacity of peripheral blood monocytes from HIV positive patients may collapse very soon after the infection.

The activity of peripheral blood monocytes from HIV positive patients was measured by the intensity of the chemoluminescence those cells emit when they ingest a foreign particle. In most patients (84%) that value was impaired. Such an alteration may occur very early in the course of the disease. The anti-p24 antibody titer was correlated with monocyte phagocytic potential as measured by the chemoluminescent value thus indicating the need for adequate monocyte activity in order to obtain antibody formation. The severity of opportunistic infections that HIV positive subjects may develop is a clear indication that their immune systems are abnormal. The most frequently affected cells are those which bear the viral receptor, the CD4 antigen. Those cells are mainly the helper T cells and monocytes. The monocytes are the immune system phagocytic cells which actively control infections, in part by the release oxidative radicals. Those radicals can easily be measured by the chemoluminescence (CL) the cells emit when they ingest a foreign particle. This study examines the CL emitted by peripheral blood monocytes from HIV-positive and control subjects while they phagocytose opsonized zymosan in vitro and correlates these values with other laboratory parameters.

Blood Bactericidal Activity↗
PubMed1992

Enhancement of HIV-specific cytotoxic T lymphocyte responses by zidovudine (AZT) treatment.

Zidovudine or 3'-azido-2'-3'-dideoxy-thymidine (AZT) is an antiviral drug widely used to treat HIV-infected patients. Because cytotoxic T lymphocytes (CTL) are thought to contribute actively to resistance against HIV-induced disease, we studied sequentially 10 HIV-infected individuals under zidovudine treatment for a period of 6-12 months. For a given patient all lymphocyte suspensions corresponding to the complete zidovudine therapy period were tested on the same day and on the same target cells. Patients were selected for expression of HLA-A2 and/or HLA-A3 class I transplantation antigen. HLA-restricted cytotoxicity specific for env, gag and nef HIV proteins was quantified for each patient at 6 week intervals. The data clearly indicated that zidovudine has a beneficial effect on the CTL response during the first 6-12 weeks of treatment, inducing cytotoxicity levels up to 100-fold stronger than base line. This effect was usually short lived. However, patients who maintained strong levels of cytotoxicity had better clinical and survival outlook than patients who had lost all detectable cytotoxic lymphocytes. It is proposed that AZT, among other effects, delays the onset of disease in HIV-infected patients by contributing to the stimulation of the HIV-specific CTL response.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Impaired proliferative capacity and abnormal cytokine profile of naive and memory CD4 T cells from HIV-seropositive patients.

Purified naive and memory CD4 T cells from healthy donors, HIV+ asymptomatic carriers and AIDS patients were examined for their proliferative activity and their pattern of cytokine secretion (IL-4, IL-6, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha)) upon stimulation with phytohaemagglutinin (PHA), phorbol myristate acetate (PMA) and cross-linked anti-CD3 MoAb, in the presence of recombinant IL-2 (rIL-2). We found a decrease in the proliferative capacity of naive CD4 T cells following stimulation with PHA and PMA, and a sharp decline in this response upon cross-linked anti-CD3 stimulation in both subsets, although it predominated in the naive subpopulation. In AIDS patients, less pronounced impairment of thymidine uptake by the naive subset was found upon PHA and cross-linked anti-CD3 MoAb stimulation. In addition, an altered secretion pattern of the different cytokines was observed, consisting of abnormal secretion of IL-6 by both naive and memory cells, an abnormal pattern of IFN-gamma secretion and frequent loss of detectable IL-4 production by HIV patients. These abnormalities were even more pronounced in AIDS patients than in the asymptomatic carriers. Overall, our results extend previous reports indicating functional impairment of memory CD4 subsets in HIV+ subjects by showing that this impairment involves naive CD4 T cells.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Natural killer (NK) cell activity during HIV infection: a decrease in NK activity is observed at the clonal level and is not restored after in vitro long-term culture of NK cells.

NK cell activity is impaired in HIV-infected patients. The mechanisms behind the altered NK functions are not clear, and conflicting data concerning NK and antibody-dependent cellular cytotoxicity (ADCC) activity have been reported. In order to investigate whether this impairment is also observed at the clonal level and whether it is related to a defect at the target cell binding and/or the post-binding level, we evaluated highly purified NK cell lines and cloned NK cells obtained from 22 HIV-infected patients at different stages of disease and compared them with normal controls for their ability to: (i) kill K-562 and U-937 cell lines using a 51Cr release assay; (ii) bind and kill K-562 and U-937 cells at the single cell binding level; (iii) release NK cytotoxic factor (NKCF), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma); (iv) kill anti-IgM preincubated Daudi cell line (ADCC activity). This study with cloned NK cells or NK cell lines from HIV-infected individuals showed: (i) a decrease in their lytic capability against target cell lines; (ii) a low ability to form conjugates with K-562 and U-937 cell lines with respect to controls; (iii) a decreased ability to kill bound target cells; (iv) low levels of released NKCF, TNF-alpha and IFN-gamma after incubation with U-937 cells. Taken together, these findings suggest that the impaired NK cell function during HIV infection is also observed at the clonal level and is related to defects both at the target and post-binding levels. However, the precise mechanisms remain to be determined. The inability to restore normal NK activity after long-term culture in the presence of high levels of recombinant IL-2 is in agreement with the hypothesis of a 'general anergic process' during HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Evaluation of residual disease in B-cell chronic lymphocytic leukemia patients in clinical and bone-marrow remission using CD5-CD19 markers and PCR study of gene rearrangements.

We evaluated minimal residual disease (MRD) in 23 CD5 + B-chronic lymphocytic leukemia (CLL) patients who achieved clinico-hematological remission confirmed by bone-marrow biopsy. MRD was evaluated by dual marker analysis flow-cytometry using CD5 and CD19 markers, and by the study of Ig heavy chain gene rearrangements using the fast polymerase chain reaction (PCR). According to our laboratory conditions patients were considered to be in complete phenotypic remission when total CD19+ cells were < 25% and the ratio of CD5 + CD19 + /CD19 + cells was < 25%. According to these strict criteria only 9 of the 23 patients were in complete phenotypic remission. In order to evaluate the sensitivity of the above method, PCR analysis of the configuration of the Ig heavy chain gene region was performed in 12 of these patients. Five of 7 patients in complete phenotypic remission retained a detectable monoclonal rearrangement of the Ig heavy chain gene. For the remaining 5 patients in partial phenotypic remission, only one failed to show a monoclonal band and this is probably explained by the presence of an unusual gene rearrangement. In conclusion, this study suggests that PCR is more sensitive than dual marker flow-cytometry for evaluation of residual disease and that it is indeed possible to achieve complete remission at the molecular level, in B-CLL. Nevertheless, we suggest a word of caution as this was a retrospective study, and samples were not assessed before treatment. Thus the possibility that apparent molecular remission might correspond to unusual gene rearrangements cannot be completely excluded in these cases.

Adult↗
PubMed1991

IgG production in hybridoma batch culture: kinetics of IgG mRNA, cytoplasmic-, secreted- and membrane-bound antibody levels.

During batch cultivation of the I.13.17. hybridoma cell line, there is a 15 to 20-fold decrease in the levels of cytoplasmic and membrane-bound mAb, and a 7 to 10-fold decrease in the cellular levels of kappa and gamma chain mRNAs, as the cells pass from the exponential into the decline phase of growth. The profile of the specific mAb production rate does not correlate with the kinetics of either the cytoplasmic mAb or the specific mRNAs throughout the culture. Flow cytometry analyses have revealed that dead cells, which account for 40 to 70% of total cells during the decline phase, might significantly interfere with the determination of cytoplasmic mAb levels of cell-lysates ELISA and with the calculation of the specific mAb production rate. Possible influences of these parameters on mAb synthesis and secretion during hybridoma batch culture are discussed.

Animals↗
PubMed1991

Serum levels of IL-2, IL-1 alpha, TNF-alpha, and soluble receptor of IL-2 in HIV-1-infected patients.

Serum levels of the interleukins (IL-1 alpha, IL-2), tumor necrosis factor-alpha (TNF-alpha), and soluble receptor of IL-2 (sIL-2R) were studied by enzyme-linked immunosorbent assay (ELISA) in 12 normal healthy controls and 52 HIV-1 seropositive patients. Results indicated that: (1) sIL-2R levels were significantly increased in most HIV-1 seropositive patients. This increase appeared to be correlated with low CD4 cell counts and with the presence of detectable levels of p25 antigen. Furthermore, initially high levels of sIL-2R appeared to be correlated with progression of disease. (2) IL-2 levels were found to be increased in about 43% of asymptomatic carriers (ASY) and subjects with lymphoadenopathy-associated syndrome (LAS) compared with 12% in the case of AIDS-related complex (ARC) and AIDS patients. (3) There was a positive correlation between serum levels of TNF-alpha and IL-1 alpha in nearly all patients. Detectable levels of both cytokines were found in 34% of ASY and LAS patients and only rarely were detectable in ARC and AIDS patients. (4) Sixteen patients in whom progression of disease was observed were studied initially and at the moment they upstaged. No significant modification of serum levels of the three cytokines and sIL-2R studied could be evidenced. It was concluded that sIL-2R could be a useful marker of disease activity and progression, though a prospective study is necessary. For IL-2, IL-1 alpha, and TNF-alpha, this study indicated the presence of variable alterations in serum levels in HIV-1-infected patients.

AIDS-Related Complex↗
PubMed1991

Serial study of CD5+ and CD5- B cell subpopulations in 335 HIV seropositive patients.

B cell subpopulations, as defined by double-labelling techniques with CD5 and CD19 monoclonal antibodies (MoAbs), were serially studied in 335 HIV-1 seropositive patients. At the time of the first consultation, no important modifications in either CD5+ or CD5- subpopulations were observed, whatever the stage of the disease. However, in 18 out of the 335 patients (5.37%), a sharp increase in B cells exceeding 20% and 300/mm3 was observed. This increase in B cells was mainly accounted for CD5-CD19+ B cell subpopulations and was associated with: (i) evolution of the disease, since only four patients presented it at their first consultation (one lymphadenopathy-associated syndrome (LAS) and three AIDS); (ii) advanced stages of disease since, at the time of B cell augmentation, two patients were staged as LAS, four as ARC and 12 as AIDS; (iii) a high incidence of non-Hodgkin's lymphomas (NHL) since three out of the 18 patients presented a histologically confirmed NHL and three others a clinical pattern compatible with this diagnosis. However, in three patients with B hyperlymphocytosis, polymerase chain reaction (PCR) studies of immunoglobulin gene rearrangement revealed the existence of a polyclonal expansion of B cells. These results justify inclusion of a pan-B cell marker in routine phenotypic studies of HIV-infected individuals, as well as the search for NHL among patients presenting this abnormality.

Antigens, CD↗
PubMed1991

Extensive analysis of lymphocyte subsets in normal subjects by three-color immunofluorescence.

In the present work, 30 normal controls were studied with 11 combinations of 3 monoclonal antibodies in order to define CD20, CD4, CD8, CD16 and CD56 subsets as well as their activation status. Our results indicated that among B cells, CD5- cells predominated (about 92%), the minor CD5+ fraction showed variations between individuals but sometimes was as high as 20% in B cells; the CD45RA+CD29- subset (naive cells) accounted for 31.56 +/- 10.03% in CD4 cells, as compared to CD4+CD29+CD45RA- (memory cells) (46.54 +/- 10.35%), while CD4+CD29+CD45RA+ (transition cells between naive and memory state) represented 9.6 +/- 5.3% as compared to double-negatives (12.3 +/- 5.24%). Some uncertainties persist in defining CD8 subsets. NK CD8 cells accounted for about 20% of total CD8 according to CD16 and CD56 expression. Cytotoxic T lymphocytes could be delineated by S6F1 (76.22 +/- 11.28% within CD8 cells), though this marker appeared to be expressed by both cytotoxic and NK cells. Phenotypic definition of suppressive CD8 cells remains uncertain despite the fact that suppressor activity was found among CD8 lymphocytes expressing CD11b and probably CD57. NK cells coexpressed CD16 and CD56 markers in about 5% of all lymphocytes, while NK cells expressing CD16 alone accounted about 6%. Exclusive expression of CD56 was found in about 5%. Finally, while activated cells characterized by DR expression represented about 4% of CD4 and 9% of CD8 cells, CD25 appeared to be poorly represented among CD4, CD8 and CD20.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1991

Establishment of long term cell lines from 2 patients with large granular lymphocyte lymphocytosis displaying an unusual phenotype.

Two long-term cell lines obtained from two cases of large granular lymphocyte lymphocytosis (LGLL) displaying an unusual phenotype are reported here. Patient n. 1 was CD2+ CD3- CD16+ CD8+ CD56- CD57- CD29+ CD45RA+, whereas patient n. 2 was CD2-CD3+ CD8+ CD16+ CD56- CD57+ CD29+ CD45RA+. The cells were large granular lymphocytes by light and electron microscopic criteria and displayed strong antibody-dependent cell mediated cytotoxicity (ADCC) and NK activity. Northern blot analysis revealed aberrant transcripts of TCR beta chains for patient n. 1, and full length TCR alpha and beta transcripts for patient n. 2. In both cases, we were able to establish a long term cell line which functionally revealed strong ADCC and NK activity. Functional implications of these 2 subpopulations are discussed.

Aged↗
PubMed1988

Autocrine secretion of tumor necrosis factor under the influence of interferon-gamma amplifies HLA-DR gene induction in human monocytes.

Recombinant interferon-gamma (IFN-gamma) induced HLA-DR gene expression in both U937 and THP-1 human monocytic cell lines, although the former was only very weakly inducible. Combination of recombinant tumor necrosis factor (TNF) and IFN-gamma resulted in a synergistic enhancement of DR mRNA and protein induction in both cell lines. TNF alone increased the constitutive expression of the DR gene in THP-1 cells. In the HLA class II-negative U937 cells, TNF used alone was not able to induce DR gene expression. Such a negative result was not due to a lack of TNF receptor expression in U937 cells, since TNF clearly induced HLA class I and TNF gene expression in this cell line. THP-1, but not U937, cells secreted TNF under the influence of IFN-gamma. Neutralization of TNF by a specific antibody decreased IFN-gamma-induced DR antigen expression in THP-1 cultures. These observations indicate that TNF is not able to directly induce DR gene expression, but rather amplifies ongoing expression of this gene, whether constitutive or induced by IFN-gamma. In the two cell lines tested, the level of DR inducibility under the influence of IFN-gamma used alone depended on a different inducibility of TNF secretion by IFN-gamma. Altogether, our observations indicate that TNF, whether exogenous or endogenously produced under the influence of IFN-gamma, amplifies DR gene expression in monocytes, a phenomenon that may provide to such antigen-presenting cells a selective sensitivity to the DR-inducing effects of IFN-gamma.

Drug Synergism↗
PubMed1988

Selective depletion of low-density CD8+, CD16+ lymphocytes during HIV infection.

Two color cytofluorometric analyses of CD3-, CD16+, Leu 19+ natural killer cells (NK) were assessed in HIV seropositive patients, high-risk seronegative homosexuals, and healthy heterosexuals. A selective depletion of lymphocytes bearing NK phenotypes was found among HIV-positive infected patients. When the CD16+ lymphocyte compartment was further dissected, lymphoid cells bearing simultaneously low cell-surface density CD8 and CD16 (Leu 11a or Leu 11c) or Leu 19 epitopes were selectively and significantly decreased. This important depletion of CD8+ NK cells, which in most cases are CD3-, accounts for the decline in low-density CD8+ lymphocytes in HIV positive group, while a significant increase occurs in their CTL pool. Furthermore, in HIV negative high-risk homosexuals, a less profound but significant reduction of this lymphocyte subset was also found. Whether the involvement of the NK compartment, especially NK cells expressing the CD8 marker, may influence the outcome of individuals infected with HIV is still an open question.

Antibodies, Monoclonal↗
PubMed1988

Comparative analysis of CD4-4B4 and CD4-2H4 lymphocyte subpopulations in HIV negative homosexual, HIV seropositive and healthy subjects.

A comparative analysis of subsets (4B4 and 2H4) within the CD4 lymphocyte subpopulation was made by double marker analysis among 23 healthy heterosexual, 16 healthy HIV seronegative high-risk homosexuals and 82 HIV seropositive subjects. Data show that the significant increase in CD4 lymphocytes observed among seronegative homosexuals corresponds mainly to an increase in CD4-4B4 positive cells while CD4-2H4 subset levels remain comparable to healthy heterosexual controls. A decrease both in CD4-4B4 and CD4-2H4, parallel to a decrease in CD4 subpopulation, was observed in asymptomatic seropositive carriers (SPC) and patients with ARC syndrome (AIDS-related complex) or AIDS (acquired immunodeficiency syndrome). Interestingly, an absolute decrease in CD4 subpopulation in patients with asymptomatic lymph node enlargement (LAS), is chiefly accounted for by a decrease in CD4-4B4 subset. The values of CD4-2H4 subset are significantly higher than those observed for SPC patients and are close to the normal values. These observations are of interest, as no differences between SPC and LAS patients could be detected when CD3, CD4 and CD8 subpopulations were studied.

Acquired Immunodeficiency Syndrome↗
PubMed1988

CD4, CD8 and NK subsets in B-CLL.

Although B-CLL is a hematological disorder characterized by clonal proliferation of B-cells, in most cases an increase in absolute numbers of T cells is observed. This increase is probably polyclonal in nature, since most data indicate that T lymphocytes are not progeny of the malignant clone in B-CLL. As CD4, CD8 and NK cells correspond to heterogeneous populations, in this work we tried to better define these subpopulations. Thus, CD4 subpopulations were displayed by using double labelling techniques into helper inducer subset (CD4+CDW29+) and suppressor inducer subset (CD4+CD45R+). CD8 subpopulations were delineated according to density expression of CD8 and reactivity with CD16 and CD11b in: suppressive cells defined by high density (HD) CD8 and reactivity with CD11b; NK cells defined by low density (LD) CD8 and binding to CD16; CTL cells by LD or HD CD8 and absence of expression of CD16 and CD11b. Our results concerning 47 normal control donors and 27 B-CLLs indicated that: although percentages of cells expressing CD3, CD4, CD8 and NK markers are decreased, absolute values of these subpopulations were increased; there exists an imbalance concerning CD4 and CD8, given by a more important increase of CD8 than CD4 subpopulations, but both are significantly augmented when compared to the normal range; within CD4 subpopulations, there is an important increase of CD4 CDW29 subset (helper inducer) whereas the CD4 CD45R (suppressor inducer) is not augmented in stage A patients and decreases in stage C patients; all the 3 identified CD8 subpopulations (NK, suppressors and CTLs) appeared to be increased; in 3 cases of clonal remission CLL studied, all T cell and NK subpopulations were recovering to normal percentages.

Antigens, Differentiation, T-Lymphocyte↗