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B Autran

Publications and source records attributed to B Autran.

At least 73 records · Page 4Linked to original sources
PubMed1998

Low CD83, but normal MHC class II and costimulatory molecule expression, on spleen dendritic cells from HIV+ patients.

Dendritic cells (DCs), which are the most potent antigen-presenting cells for T lymphocytes, are targets for HIV in vitro and in vivo. Antigen presentation by DCs has been suggested to be impaired during HIV infection; however, the extent to which DCs from HIV+ individuals are altered, particularly in lymphoid organs where T cell stimulation takes place, is not clear. To address this question, the levels of expression of functionally important molecules by spleen DCs from HIV+ patients (n = 6), and HIV- organ donors (n = 5) were compared. By rare event analysis of flow cytometry data, spleen DCs from HIV+ patients were not depleted, representing 0.6 +/- 0.4% of spleen mononuclear cells compared with 0.8 +/- 0.5% in HIV- spleens. Fresh HIV+ spleen DCs were MHC II+ and weakly CD86+CD40+, but negative for CD83 and CD80, and hence had a normal phenotype, showing no signs of in vivo activation. After 24 hr of culture, they upregulated the expression of MHC II, CD40, CD80, and CD86 to levels just as high as those on DCs from organ transplant donors. However, cultured DCs from HIV+ spleens showed lower expression of CD83, compared with DCs from HIV- spleens. The biological significance of this observation will be appreciated further when the function of this molecule is better known. These results suggest that putative defects in antigen presentation by DCs from HIV+ patients are not related to the surface expression of MHC II, CD40, CD80, or CD86.

Antigens, CD↗
PubMed1998

Arthralgias and cryoglobulinemia during protease inhibitor therapy in a patient infected with human immunodeficiency virus and hepatitis C virus.

We present the case of a woman who had a chronic infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). She developed severe polyarthralgias associated with type II mixed cryoglobulinemia during therapy with an HIV-1 protease inhibitor. This therapy resulted in a dramatic increase in her CD4+ T cell count, from 70/mm3 to 567/mm3, which was composed of a high proportion (88%) of naive CD45RA+ CD62L+ cells, together with a recovery of her CD4+ T cell reactivity to antigenic stimulation. This may suggest that rapid recovery of immune competence in the CD4+ T helper subset might participate in the development of immunopathologic events such as this patient's cryoglobulinemia.

Arthralgia↗
PubMed1998

Monocyte-derived dendritic cells have a phenotype comparable to that of dermal dendritic cells and display ultrastructural granules distinct from Birbeck granules.

Most monocyte-derived dendritic cells (DC) display CD1a, like Langerhans cells (LC) and some dermal DC, but their relationship with these skin DC remains unclear. To address this issue, we studied the expression of different antigens characteristic of skin DC and of monocyte/macrophages in CD1a+ and CD1a- monocyte-derived DC. Their phenotype indicated that they may be related to dermal DC rather than to LC, i.e., they were all CD11b-positive, and 72% were Factor XIIIa-positive, but they did not express E-cadherin nor VLA-6. It is interesting that CD1a+ and CD1a-cells showed intracytoplasmic granules that were different from LC Birbeck granules. These phenotypical and ultrastructural features are comparable to those of CD14-derived DC obtained from cord blood precursors [C. Caux et al. J. Exp. Med. 184, 695-706]. These results show a close relationship between these two in vitro models, which are both related to dermal DC.

Antigens, CD↗
PubMed1998

Pulmonary infections associated with systemic capillary leak syndrome attacks in a patient with hypogammaglobulinemia.

Systemic capillary leak syndrome (SCLS) is a rare disorder of unknown etiology, characterized by recurrent hypovolemic shock attacks associated in most cases with a serum monoclonal immunoglobulin. Prophylactic therapy is usually disappointing and the outcome is often fatal. We report on a patient with recurrent hypovolemic shocks consistent with the diagnosis of SCLS associated with severe serum panhypogammaglobulinemia but no detectable monoclonal immunoglobulin or B cell proliferation. Attacks were often preceded by severe respiratory infections. Both infections and attacks were successfully prevented by i.v. gammaglobulin replacement. Further evaluation is needed to assess the efficacy of i.v. gammaglobulins in patients with SCLS but without hypogammaglobulinemia.

Adult↗
PubMed1998

Perturbation of CD4+ and CD8+ T-cell repertoires during progression to AIDS and regulation of the CD4+ repertoire during antiviral therapy.

The T-cell antigen receptor (TCR) repertoire was studied longitudinally by analyzing the varying lengths of the beta chain CDR3 hypervariable region during the course of HIV-1 infection and following combination antiretroviral therapy. Drastic restrictions in CD8+ T-cell repertoire usage were found at all stages of natural progression and persisted during the first six months of treatment. In contrast, significant CD4+ T-cell repertoire perturbations were not found in early stages of infection but correlated with progression to AIDS. Out of ten patients presenting with pretreatment perturbations, normalization of the CD4+ repertoire was observed in eight good responders, but not in two cases of unsuccessful therapy. These results indicate that, besides CD4+ cell count rise, an efficient control of HIV replication may allow qualitative modifications of the CD4+ repertoire balance.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Epidermodysplasia verruciformis-like eruption complicating human immunodeficiency virus infection.

Three human immunodeficiency virus (HIV)-infected patients presented with disseminated pityriasis versicolor-like skin lesions. Histological examination showed features characteristic of epidermodysplasia verruciformis (EV). Hybridization studies demonstrated the presence of human papillomavirus (HPV) type 5 (HPV5) DNA in two patients and HPV20 in one. A relative increase in CD8+, CD57+ cells, which are known to inhibit cell-mediated cytolysis, was observed in all patients. HLA-DQB 0301 haplotype, which has been associated with EV, was detected in two patients. The findings suggest that infection with EV-associated HPV types can complicate HIV infection. Both cellular immune defects and a hitherto unknown genetic background might explain the occurrence of EV in HIV-infected patients.

AIDS-Related Opportunistic Infections↗
PubMed1998

No evidence for abnormal immune activation in peripheral blood T cells in patients with hepatitis C virus (HCV) infection with or without cryoglobulinaemia. Multivirc Group.

The aim of this study was to investigate the peripheral blood lymphocyte (PBL) phenotypes and T cell repertoire in patients with HCV infection, with or without mixed cryoglobulinaemia (MC). The patients were: Group 1, 23 patients with HCV infection and MC; Group 2, 14 patients with HCV infection but without MC; Group 3, 10 patients with symptomatic essential MC. Twenty healthy blood donors were used as controls. Blood lymphocyte counts were determined, and flow cytometry was used to measure proportions of B cells (CD19+), natural killer (NK) cells (CD16+CD56+), T cells (CD3+), CD4+ T cell subsets (memory CD4+CD45RO+; naive CD4+CD45RO-; Th0/Th2CD4+CD7-; activated CD4+CD25+), and CD8+ T cell subsets (immunoregulatory CD8+CD57+; cytotoxic CD8+S6F1+, activated CD8+CD25+). Bias in the usage of T cell receptor (TCR) Vbeta chains was studied in a subgroup of 10 representative patients of Group 1 using a polymerase chain reaction (PCR) analysis of the Vbeta segments with a series of 20 oligonucleotides specific for the Vbeta families. The three groups were comparable for blood lymphocyte counts, and we observed no abnormal repartition of the following PBL subsets: T cells (CD3+), CD4+ and CD8+ subpopulations, B cells (CD19+), and the NK cells (CD16+56+). In none of the groups could we observe lymphocyte ex vivo activation as assessed by the normal expression of the activation cell markers: CD25 on CD4+ or CD8+ T cells, or CD5 on B cells. The repartition of naive and memory (CD45RO-/RO+) CD4+ T cells was normal and we did not observe any amplification of the CD4+CD7- T cell subset differentiated in vivo in Th0/Th2 cells. There was no significant amplification of cytotoxic (SF6+) and immunoregulatory (CD57+) CD8+ T cells in HCV patients with or without MC. Finally, the usage of Vbeta families in the TCR repertoire was normal in the patients tested. In patients with chronic HCV infection, with or without MC, we did not find any significant expansion or abnormal activation of T, B and NK cell subsets, dysbalance of the naive/memory subsets, or expansion of the Th0/Th2 subpopulation. These findings differ from the profound immune alterations that are observed in other chronic infections such as HIV or Epstein-Barr virus. Although this study was restricted to the peripheral blood, it suggests that in chronic HCV infection, MC is not the consequence of a chronic activation or dysregulation of the peripheral blood immune cells.

Adult↗
PubMed1998

CD8hi+CD57+ T lymphocytes are enriched in antigen-specific T cells capable of down-modulating cytotoxic activity.

Major expansions of CD8hi+CD57+ T lymphocytes frequently occur during human immunodeficiency virus (HIV) infection and after transplantation. To investigate mechanisms of such cell expansion, we compared the activation and functional status of CD8hi+CD57+ and CD57-peripheral blood lymphocytes (PBL) from normal, bone marrow transplantation (BMT) and HIV+ donors. The CD8hi+CD57+ PBL from BMT and HIV+ donors preferentially displayed CD38 and HLA-DR activation markers without correlation between CD8hi+CD57+ percentages and HIV load, the CD45RA+ isoform in all ex vivo conditions but acquired CD45RO after in vitro expansion, CD11b and CD11c in BMT and HIV+ donors but decreased expression of CD62-L, VLA-2 and VLA-6. The CD8hi+CD57+ cells were positive for perforin and granzyme B and spontaneously mediated cytolytic activity in a CD3-redirected assay. In contrast the inhibitor of cytolytic functions (ICF) produced by CD8hi+CD57+ cells down-modulated the CD3-redirected cytolytic activity but only at low levels of CD3 cross-linking. While CD3-triggering induced a low, if any, short-term proliferation of CD8+CD57+ cells, this subset could be amplified after long-term stimulation either with mitogens or with HIV antigens, thereby enriched in HIV-specific T cells producing tumor necrosis factor-alpha. Altogether these data suggest that CD8hi+CD57+ cells represent a terminal differentiation state of activated effector cytotoxic T lymphocytes which are enriched in antigen-specific T cells and down-modulate their own cytolytic potential, thus participating in a negative control of effector cell functions during persistent viral infections or transplantations.

CD57 Antigens↗
PubMed1997

Expansion of CD4+CD7- T cells, a memory subset with preferential interleukin-4 production, after bone marrow transplantation.

BACKGROUND: Inadequate reconstitution of CD4+ lymphocyte and interleukin (IL)-2 production defect are observed after bone marrow or peripheral blood stem cell transplantation (SCT). METHODS: We studied immune reconstitution after SCT in 33 consecutive patients who received allogeneic SCT (17 patients) or autologous SCT (16 patients). The aims were to assess the regeneration of the CD4+ T-cell subset with regard to helper cell differentiation. CD4+ T-cell subset regeneration and expansion of the CD4+CD7- subset were studied by immunofluorescence analysis. CD4+CD7- cell cytokine secretion was analyzed after cell sorting and costimulation of the CD3 and CD28 pathways, in enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction assays. RESULTS: We report a relative expansion of the CD4+CD7- subset within CD4+ T cells, detected as early as 1 month after bone marrow transplantation and decreasing after day 60. CD4+CD7- T cells preferentially expressed CD45RO and activation markers such as CD57, CD25, and HLA-DR. No relationship was observed between the CD4+CD7- expansion and transplant-related complications. We observed no significant IL-2 production in supernatants from sorted CD4+CD7- T cells, whereas IL-4 levels were comparable to those produced by cells from normal individuals. Autologous CD4+CD7+ cells showed little, if any, IL-4 production, and IL-2 production was lower than that by normal CD4+CD7+ T cells. Reverse transcription-polymerase chain reaction assays showed similar amounts of interferon-gamma transcripts in the two subsets; tumor necrosis factor-alpha, IL-4, and IL-10 transcripts were detected in CD4+CD7- T cells but not in their CD4+CD7+ counterparts. CONCLUSIONS: These data confirm the IL-2 production defect after bone marrow transplantation and suggest that the CD4+CD7- T-cell subset might be preferentially involved in the enhanced production of IL-4 and low production of IL-2. These data show that the early immune reconstitution in CD4+ T cells after SCT preferentially involves memory T cells with a Th0/Th2 differentiation that might participate in the T-helper cell defect.

Adult↗
PubMed1997

Interferon beta transduction of peripheral blood lymphocytes from HIV-infected donors increases Th1-type cytokine production and improves the proliferative response to recall antigens.

We are developing a gene therapy method of HIV infection based on the constitutive low production of interferon (IFN) beta. Peripheral blood lymphocytes (PBL) from HIV-infected patients at different clinical stages of infection were efficiently transduced with the HMB-HbHuIFNbeta retroviral vector. The constitutive low production of IFN-beta in cultured PBL from HIV-infected patients resulted in a decreased viral production and an enhanced survival of CD4+ cells, and this protective effect was observed only in the PBL derived from donors having a CD4+ cell count above 200 per mm3. In IFN-beta-transduced PBL from healthy and from HIV-infected donors, the production of the Th1-type cytokines IFN-gamma and interleukin (IL)-12 was enhanced. In IFN-beta-transduced PBL from HIV-infected donors, the production of IL-4, IL-6, IL-10, and tumor necrosis factor alpha was maintained at normal levels, contrary to the increased levels produced by the untransduced PBL. The proliferative response to recall antigens was partially restored in IFN-beta-transduced PBL from donors with an impaired antigen response. Thus, in addition to inhibiting HIV replication, IFN-beta transduction of PBL from HIV-infected donors improves several parameters of immune function.

CD4 Lymphocyte Count↗
PubMed1997

Analysis by flow cytometry of tyrosine-phosphorylated proteins in activated T-cell subsets on whole blood samples.

Tyrosine phosphorylation of cellular proteins is a critical early event in the T-cell activation process induced by the antigenic peptide or monoclonal antibodies specific for the CD3 T-cell receptor (TCR) complex. Phosphoproteins are currently detected by Western blotting experiments or, recently, by labelling intracellular proteins with an antiphosphotyrosine monoclonal antibody and flow cytometric analysis (Farahi Far et al.: Cytometry 15:327-334, 1994; Vuillier et al.: J Immunol Methods 185:43-56, 1995). Here, we describe improvements of these latter methods in order to study selectively the CD3-TCR signaling pathway of patients with immunodeficiency diseases or lymphopenia. This new technique quantifies tyrosine-phosphorylated proteins in in vitro-activated T-cell subsets directly on whole blood samples. The stimulation of the CD3-TCR complex induces a specific and significant increase in the phosphotyrosine fluorescence intensity in both CD4 and CD8 subpopulations. The simplicity and the good reproducibility of this method make it particularly convenient for laboratory routine evaluation, and the use of very small volumes of blood is well adapted to the study of immunodepressed patients. Moreover, this technique allows the detection of early molecular defects of the CD3-TCR signal-transduction pathway.

Adult↗
PubMed1997

Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease.

Highly active antiretroviral therapy (HAART) increases CD4(+) cell numbers, but its ability to correct the human immunodeficiency virus (HIV)-induced immune deficiency remains unknown. A three-phase T cell reconstitution was demonstrated after HAART, with: (i) an early rise of memory CD4(+) cells, (ii) a reduction in T cell activation correlated to the decreasing retroviral activity together with an improved CD4(+) T cell reactivity to recall antigens, and (iii) a late rise of "naïve" CD4(+) lymphocytes while CD8(+) T cells declined, however, without complete normalization of these parameters. Thus, decreasing the HIV load can reverse HIV-driven activation and CD4(+) T cell defects in advanced HIV-infected patients.

Adult↗
PubMed1997

Dynamics of HIV variants and specific cytotoxic T-cell recognition in nonprogressors and progressors.

Infection with the human immunodeficiency virus (HIV) results in a disease characterized by a rapid viral replication, immunodeficiency and chronic immune activation. The vigorous polyspecific cytotoxic T-cell (CTL) response directed against multiple HIV epitopes reduces HIV-infected cell numbers, although unable to eradicate the virus. The plasticity of the specific CTL repertoire ensures adaptation to the high rate of viral variation that can be found in CTL epitopes of several HIV-1 proteins. However, viral persistence occurs despite continuous CTL recognition and although functional importance of conserved sites in the different HIV proteins may impose constraints to viral variation. In the reverse transcriptase (RT) which is a major target for antiretroviral therapy, the impact of the continuous pressure of drug therapy is more obvious than that of the CTLs. Shifts in immunodominant RT regions seem to allow the maintenance of the HIV-1 RT CTL recognition with disease progression and antiretroviral therapy. In respect to new highly active drug combinations, understanding the capacity of virus-specific CTLs to control residual viral variants seems very important and may allow development of efficient immunotherapies to prevent drug-induced viral resistance.

Adaptation, Physiological↗
PubMed1997

The SCID mouse mutant: definition and potential use as a model for immune and hematological disorders.

Mice homozygous for a SCID mutation (SCID mice) are severely deficient in T and B lymphocytes. The absence of effector T and B cells has encouraged investigators to attempt engraftment of SCID mice with human fetal tissues, mature lymphocytes, hematopoietic progenitors and tumors. SCID mice can be reconstituted with human lymphocytes and are of interest for studying normal and abnormal lymphocyte development and function. SCID mice are also providing an in vivo model of infectious diseases. In addition, SCID mice readily support normal and pathologic human hematopoiesis differentiation and is useful for testing innovative hematological disease therapy. SCID mice with a fully functional human immune or hematopoietic system therefore seem to be extremely valuable for biomedical research.

Animals↗
PubMed1997

Studies of T cell reconstitution after hematopoietic stem cell transplant.

Hematopoietic stem cell (HSC) transplantation, whatever its conditions, is associated with an increased risk of infections and tumoral complications, because of a delayed immune reconstitution. T-cell regeneration has been mostly investigated and appears to come more from graft and/or host mature T-cells, rather than from the differentiation/maturation of reinfused progenitors. In allogeneic setting, the immune defect is enhanced by the immune host/donor conflict and the use of prophylactic or curative immunosuppressive therapy. The tools used for studying post-transplant immunity are the following: immunophenotyping (kinetics and alterations of lymphocyte subset reconstitution), functional studies of T cell proliferation, cytokine production, cytotoxicity and signal transduction, as well as studies of T cell repertoire diversity. The CD4/CD8 cell immunophenotyping might be enough for routine clinical evaluation, allowing an adapted prophylaxis of opportunistic infections in those immune-suppressed patients, while functional assays might be useful to evaluate the persistence overtime of defects in immune reconstitution. These overall assays are useful both for basic and clinical research and allow better understanding in the mechanisms for T cell regeneration in the diverse types of HSC transplants performed nowadays particularly after graft of purified HSC where immune reconstitution remains a key question.

Hematopoietic Stem Cell Mobilization↗
PubMed1997

[Development of an anti-HIV gene therapy based on the antiviral properties of beta interferon].

The aim of our work is to explore the use of IFN-beta for gene therapy in the HIV-infection. Transduction of various HIV target cells with a retroviral vector that carries the Hu-IFN-beta coding sequence under constitutive low expression control, confers resistance to HIV without affecting cell replication or function. After transduction, lymphocytes from HIV-infected patients develop resistance to the endogenous virus, provided the cells are derived from individuals with a CD4 cell count higher than 200 per mm3.

Anti-HIV Agents↗