Varicella-zoster virus-specific cell-mediated immune responses in HIV-infected adults.

The incidence of herpes zoster remains high in HIV-infected patients despite the use of combined antiretroviral therapy (cART). We wished to assess varicella-zoster virus (VZV)-specific cell-mediated immune (CMI) responses in HIV-infected adults on cART. VZV-specific CMI responses were assessed using lymphocyte proliferative responses, cytokine production (IL-2, TNF-α, and IFN-γ), and interferon-γ ELISPOT assays in 103 HIV-infected adults and 30 healthy controls.

Autoimmunity in common variable immunodeficiency: correlation with lymphocyte phenotype in the French DEFI study.

Common variable immunodeficiency (CVID) is the most frequent clinically expressed primary immunodeficiency in adults and is characterized by primary defective immunoglobulin production. Besides recurrent infectious manifestations, up to 20% of CVID patients develop autoimmune complications. In this study, we took advantages of the French DEFI database to investigate possible correlations between peripheral lymphocyte subpopulations and autoimmune clinical expression in CVID adult patients.

Remission of severe CD8(+) cytotoxic T cell skin infiltrative disease in human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy.

Background: A CD8 cutaneous lymphoinfiltrative disease has been described in human immunodeficiency virus (HIV)-infected patients presenting with a severe erythroderma. The true nature of this severe skin infiltrative disorder is still elusive. Although some clinical features of this syndrome have raised the hypothesis of its malignant nature in initial observations, several studies have provided stronger support to the hypothesis that it is a reactive pseudotumoral process.

B-cell and T-cell phenotypes in CVID patients correlate with the clinical phenotype of the disease.

Background: Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by recurrent infections and defective immunoglobulin production.

Methods: The DEFI French national prospective study investigated peripheral T-cell and B-cell compartments in 313 CVID patients grouped according to their clinical phenotype, using flow cytometry.

Results: In patients developing infection only (IO), the main B-cell or T-cell abnormalities were a defect in switched memory B cells and a decrease in naive CD4(+) T cells associated with an increase in CD4(+)CD95(+) cells.

Cellular CD4 T cell responses to the diphtheria-derived carrier protein of conjugated pneumococcal vaccine and antibody response to pneumococcal vaccination in HIV-infected adults.

Background: The French National Agency for AIDS and Viral Hepatitis Research (ANRS) 114 Pneumovac trial showed that a strategy combining a 7-valent pneumococcal conjugate vaccine (PCV) prime at week 0 followed by a 23-valent pneumococcal polysaccharide vaccine (PPV) boost at week 4 enhances the frequency and magnitude of immunoglobulin (Ig) G responses against Streptococcus pneumoniae polysaccharides (SPPs) compared with PPV alone. CD4 T cell responses specific to the diphtheria-derived carrier protein CRM(197) were evaluated.

Methods: Lymphocyte proliferative responses (LPRs) and T(H)1 cytokine T cell responses against the diphtheria-derived carrier protein CRM(197) contained in the PCV were investigated at weeks 0, 4, and 24.

Long-term immune deficiency after allogeneic stem cell transplantation: B-cell deficiency is associated with late infections.

Immune reconstitution was analyzed in 140 consecutive patients who were 2-year disease-free and who underwent myeloablative allogeneic transplantation. A CD4 and CD8 defect was observed involving naive, terminally differentiated, memory and competent cells and above limits values for activated subsets. Natural killer cells normalize at six months while we observed expansion of CD19(+)/CD5(+) B cells after three months and a persisting defect of memory B cells.

Late-onset combined immune deficiency: a subset of common variable immunodeficiency with severe T cell defect.

Background: Common variable immunodeficiency (CVID) is a primary immune deficiency defined by defective antibody production. In most series, a small proportion of patients present with opportunistic infections (OIs).

Methods: The French DEFI study has enrolled patients with primary hypogammaglobulinemia and allows a detailed clinical and immunologic description of patients with previous OIs and/or at risk for OIs.

Acute graft-versus-host disease transiently impairs thymic output in young patients after allogeneic hematopoietic stem cell transplantation.

Long-term T-cell reconstitution after hematopoietic stem cell transplantation (HSCT) is dependent on patient thymic function and affected by graft-versus-host disease (GVHD). To assess the impact of acute GVHD (aGVHD) on thymic function, we followed a cohort of 93 patients who received HSCT from a human histocompatibility leukocyte antigen-identical sibling, mainly for hematologic malignancies. Thymic output was measured by signal-joint T-cell receptor excision circles (sjTREC) real-time polymerase chain reaction.

Restoration of Toxoplasma gondii-specific immune responses in patients with AIDS starting HAART.

Objective: To study the kinetics and identify factors associated with Toxoplasma-specific immune responses in patients with AIDS starting antiretroviral therapy.

Methods: A prospective study of 38 HIV-infected patients seropositive for Toxoplasma who started antiretroviral therapy with CD4 T cells less than 200 cells/microl. T-cell and B-cell phenotypes, anti-Toxoplasma antibodies titers, Th-1 and Th-2 cytokine production and lymphocyte proliferative responses (LPRs) to Toxoplasma were assessed over 12 months.

An unusual CD56(bright) CD16(low) NK cell subset dominates the early posttransplant period following HLA-matched hematopoietic stem cell transplantation.

The expansion of the cytokine-producing CD56(bright) NK cell subset is a main feature of lymphocyte reconstitution after allogeneic hematopoietic stem cell transplantation (HSCT). We investigated phenotypes and functions of CD56(bright) and CD56(dim) NK subsets from 43 HLA-matched non-T cell-depleted HSCT donor-recipient pairs. The early expansion of CD56(bright) NK cells gradually declined in the posttransplant period but still persisted for at least 1 year and was characterized by the emergence of an unusual CD56(bright)CD16(low) subset with an intermediate maturation profile.

Infections in 252 patients with common variable immunodeficiency.

Background: Common variable immunodeficiency is characterized by recurrent infections and defective immunoglobulin production.

Methods: The DEFI French national study prospectively enrolled adult patients with primary hypogammaglobulinemia. Clinical events before inclusion were retrospectively analyzed at that time.

Primary Epstein-Barr virus infection with pneumonia transmitted by allogeneic bone marrow after transplantation.

We report a case of primary Epstein-Barr virus infection with lung involvement occurring 1 month after bone marrow transplantation. The transplant recipient had serological test results that were negative for Epstein-Barr virus before transplantation. The virus must have been transmitted by the donor's bone marrow, which was positive for Epstein-Barr virus.

Kaposi's sarcoma-associated herpesvirus viremia is associated with the progression of classic and endemic Kaposi's sarcoma.

In order to gain further insight on the role of Kaposi's sarcoma-associated herpesvirus (KSHV) in classic and endemic Kaposi's sarcoma (KS) pathogenesis, we aimed to determine (i) whether KSHV is detectable in peripheral blood mononuclear cells (PBMCs), (ii) which PBMCs subpopulation harbor the virus, (iii) which clinical, histologic, and immunologic parameters are associated with KSHV viremia in a population of classic and endemic KS. KSHV viremia and various immunologic parameters were screened on 81 patients. KSHV viremia was positive in 58% of the patients.

Failure of rituximab in human immunodeficiency virus-associated multicentric Castleman disease.

Two human immunodeficiency virus-infected patients who needed etoposide therapy to control exacerbations of Castleman disease received four infusions of rituximab. Clinical and virologic relapses with increased blood human herpesvirus-8 DNA levels occurred in both patients 4 and 24 weeks later and were associated with a worsening of Kaposi sarcoma.

[Treatment interruption in 30 HIV-infected patients with successful viral suppression under highly active antiretroviral treatment].

Objective: To evaluate clinical and laboratory results in HIV-infected patients with complete viral suppression under HAART (highly active antiretroviral treatment) for whom treatment was interrupted and to identify risk factors associated with prolonged (i.e., successful) treatment interruption.

Therapeutic immunization with a human immunodeficiency virus (HIV) type 1-recombinant canarypox vaccine in chronically HIV-infected patients: The Vacciter Study (ANRS 094).

This open single-arm study evaluated whether the administration of an HIV-recombinant canarypox vaccine (vCP1433) in highly active antiretroviral therapy (HAART)-treated patients chronically infected with HIV was safe, immunogenic and associated with prolongation of treatment discontinuation: 48 patients received four monthly vCP1433 injections and stopped HAART. Immunization was safe. HIV-p24-specific lymphoproliferative responses (LPR), significantly increased in the whole group after two injections but decreased thereafter, HIV-gag-specific CD8 T cells were boosted in 55% patients tested.

Analysis of immune reconstitution after autologous bone marrow transplantation in systemic sclerosis.

Objective: To analyze hematopoietic and immune reconstitution after autologous hematopoietic stem cell transplantation (HSCT) in 7 patients with systemic sclerosis (SSc).

Methods: Two groups of patients were retrospectively constituted according to whether they had a favorable clinical response (group A; n = 4) or no response or a relapse of disease (group B; n = 3) after HSCT. Immune reconstitution was analyzed every 3 months using lymphocyte immunophenotyping, alpha/beta T cell receptor (TCR) diversity analysis, and ex vivo thymic function analysis by quantification of TCR rearrangement excision circles (TRECs).

Prognostic value of pretransplantation host thymic function in HLA-identical sibling hematopoietic stem cell transplantation.

Thymic function is critical for immune reconstitution after hematopoietic stem cell transplantation (HSCT). We evaluated recipient thymic function before HSCT by quantifying T-cell receptor excision circles (TRECs) in pretransplantation peripheral blood lymphocytes from 102 patients who received HSCs from an HLA-identical sibling for malignant (n = 87) or nonmalignant diseases (n = 15). Median TREC value before transplantation was 257 TRECs per 150,000 CD3+ cells (range, 0-42,746).

Epstein-Barr virus (EBV) reactivation in allogeneic stem-cell transplantation: relationship between viral load, EBV-specific T-cell reconstitution and rituximab therapy.

Background: Monitoring of Epstein-Barr virus (EBV) reactivation after allogeneic hematopoietic stem-cell transplantation markedly improved with quantitative real-time polymerase chain reaction amplification of EBV DNA and visualization of EBV-specific CD8+ T cells with peptide-human leukocyte antigen (HLA) class I tetramers. We decided to combine these methods to evaluate posttransplant EBV reactivation and rituximab therapy.

Methods: We followed 56 patients treated with an HLA-genoidentical sibling (n=32), an HLA-matched unrelated donor (MUD, n=19), or an unrelated cord-blood transplant (n=5).

IL-2 therapy and thymic production of naive CD4 T cells in HIV-infected patients with severe CD4 lymphopenia.

Objectives: IL-2 therapy increases memory and naive CD4 T cells in HIV-infected patients, but its effect on thymopoiesis is unknown. To investigate this effect, we quantified T-cell receptor rearrangement excision circles (TREC) in CD4 T cells from lymphopenic AIDS patients treated with highly active antiretroviral therapy and IL-2.

Methods: CD4 cell subsets were evaluated by flow cytometry using anti-CD45RO/RA, CD62L, Ki67 and CD95 monoclonal antibodies.

Peripheral blood lymphocyte subset counts in patients with dermatomyositis: clinical correlations and changes following therapy.

Lymphocytopenia has been reported in patients with connective tissue diseases, including dermatomyositis (DM). However, the risk of infectious complications and the changes of lymphocytic subsets during treatment have been poorly investigated in these patients. We investigated the alterations of peripheral blood lymphocyte counts in patients with DM.

Autologous bone marrow transplantation in the treatment of refractory systemic sclerosis: early results from a French multicentre phase I-II study.

Haematopoietic stem cell transplantation (HSCT) has been proposed for refractory autoimmune diseases, including systemic sclerosis (SSc). A sequential Bayesian phase I-II clinical trial was conducted in SSc patients to assess the feasibility, the tolerance and the efficacy of autologous HSCT. Peripheral blood stem cells (PBSC) were collected using cyclophosphamide (4 g/m2) and recombinant human granulocyte colony-stimulating factor (5 micro g/kg/d) and reinfused after positive CD34+ selection.

Functional modulation of expanded CD8+ synovial fluid T cells by NK cell receptor expression in HLA-B27-associated reactive arthritis.

The aim of this study was to determine whether NK cell receptor (NKR) expression could modulate cytotoxicity of oligoclonal CD8+ T cells present in the synovial fluid (SF) of HLA-B27-reactive arthritis (ReA) patients, especially in a TCRBV1 population shared among different patients and cytotoxic toward HLA-B27. A CD8+ T cell line, two TCRBV1 lines and clones were isolated from the SF of an HLA-B27+ ReA patient, and tested with mAb specific for Ig-like (KIR2DL1, KIR2DL2, KIR3DL1 and ILT2) and CD94 C-type lectin NKR. Transcripts for NKG2 subunits (NKG2A-2E) associated with CD94 were also evaluated.

A broad T-cell repertoire diversity and an efficient thymic function indicate a favorable long-term immune reconstitution after cord blood stem cell transplantation.

Cord blood (CB) is used increasingly as a source of hematopoietic stem cells because of a lower risk of acute and chronic graft-versus-host disease (GVHD). However, there is some concern regarding the ability to adequately reconstitute host immune response due to the immaturity and naivety of CB T cells. This study was designed to evaluate T-cell reconstitution using combined approaches of phenotyping, analysis of alphabeta T-cell receptor (TCR) diversity, and assessment of ex vivo thymic function by measuring TCR rearrangement excision circles (TRECs).