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Biomedical subjects

V Barnaba

Publications and source records attributed to V Barnaba.

At least 55 records · Page 3Linked to original sources
PubMed1992

Transferrin receptor mediates uptake and presentation of hepatitis B envelope antigen by T lymphocytes.

Human activated T lymphocytes expressing class II molecules are able to present only complex antigens that bind to their own surface receptors, and thus can be captured, internalized, and processed through the class II major histocompatibility complex processing pathway. We have used the antigen-presenting T cell system to identify the viral receptor used by hepatitis B virus (HBV) to enter cells, as well as the sequence of HB envelope antigen (HBenvAg) involved in this interaction. Results show that both CD4+ and CD8+ T clones can process and present HBenvAg to class II-restricted cytotoxic T lymphocytes and that the CD71 transferrin receptor (TfR) is involved in efficient HBenvAg uptake by T cells. Moreover, we provide evidence that the HBenvAg sequence interacting with the T cell surface is contained within the pre-S2 region. Since TfR is also expressed on hepatocytes, it might represent a portal of cellular entry for HBV infection. This system of antigen presentation by T cells may serve as a model to study both lymphocyte receptors used by lymphocytotropic viruses and viral proteins critical to bind them.

Amino Acid Sequence↗
PubMed1992

Tumor necrosis factor-alpha and interferon-gamma synthesis by cerebrospinal fluid-derived T cell clones in multiple sclerosis.

T cell clones derived from cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) were analysed for their capacity to produce interleukin 2 (IL-2), interleukin 4 (IL-4), interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). They were also compared with liver-infiltrating T cell clones from patients with chronic active hepatitis. All the CSF T clones (both CD4+ and CD8+) produced large amounts of IFN-gamma and particularly of TNF-alpha, that was synthesized in a significantly larger amount than compared clones. Moreover, they were capable of secreting IL-2, but not IL-4. From our results, we conclude that first, the CSF CD4+ T clones could constitute a subset with functional properties similar to the T helper 1 (Th1)/inflammatory cell subset of the mouse; and second, the large amounts of TNF produced by CSF T cell clones strongly suggests a significant role for this cytokine as well as of IFN-gamma in MS immunopathogenesis.

Adult↗
PubMed1992

T cell recognition of hepatitis B envelope proteins.

We have studied the T-cell processing pathways of Hepatitis B antigens and the role of specific B lymphocytes. It could be shown that some form of processing by specific B cells is required for class I CTLs. This mechanism differs from class II endosomal processing. In addition, it could be shown that lysis of HBsAg-specific B cells may be partly responsible for chronic HBV carrier states.

B-Lymphocytes↗
PubMed1992

Tumour necrosis factor-alpha synthesis by cerebrospinal-fluid-derived T cell clones from patients with multiple sclerosis.

T-cell clones derived from the CSF (cerebrospinal fluid) of MS (multiple sclerosis) patients have been analysed for the production of interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2) and interleukin-4 (IL-4). Each CSF-T clone (both CD4+ and CD8+) produced substantial amounts of IFN-gamma and especially TNF-alpha compared with autologous peripheral T clones and liver-infiltrating T clones from patients with chronic active hepatitis. The large quantities of TNF produced by CSF-T cell clones suggest an important role for this cytokine in MS immunopathogenesis.

Adult↗
PubMed1991

Enhanced production of interferon-gamma by T lymphocytes cloned from rejected kidney grafts.

Seventy-seven T cell clones were generated from cell blasts infiltrating rejected kidney allografts. All clones, either CD4 or CD8, displayed cytolytic activity evaluated by lectin-dependent cell-mediated cytotoxicity (LDCC) and natural killer activities. Furthermore, both types of clones were able to produce IFN-gamma following PHA stimulation. These data suggest that the graft infiltrate is characterized by T cell clones with cytolytic potential responsible for the killing of graft cells. The production of IFN-gamma, enhancing the class II MHC expression, may amplify the recipient immune response.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1991

Immunology of hepatocellular carcinoma.

The immune surveillance theory continues to remain a powerful force in cancer research and therapy despite the varying degrees of enthusiasm from both its supporters and critics. The role of both specific and non-specific immune responses in the host's defense against hepatocellular carcinoma is presented as well as the possibilities of immune-system manipulation for the prevention and therapy of this tumour.

Antibodies, Monoclonal↗
PubMed1991

Tumour necrosis factor-alpha synthesis by cerebrospinal-fluid-derived T cell clones from patients with multiple sclerosis.

T cell clones derived from cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) were analysed for their ability to produce interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2) and interleukin-4 (IL-4). The CSF-T clones were compared for their ability to produce cytokines with autologous peripheral T clones and with liver-infiltrating T cell clones from patients with chronic active hepatitis. IL-4 production was also compared with that by peripheral T clones derived from atopic patients. All the CSF-T clones (both CD4+ and CD8+) produced large amounts of IFN-gamma and particularly of TNF-alpha. These cytokines were synthesized in significantly larger amounts by CSF T clones than by reference clones. Moreover, they were capable of secreting IL-2, but not IL-4. We conclude that the CSF-CD4+ T clones could constitute a subset with functional properties similar to those of T helper 1 (Th1)inflammatory cells of the mouse; and that the large amounts of TNF produced by CSF T cell clones strongly suggest a significant role for this cytokine in MS immunopathogenesis.

Adult↗
PubMed1990

Selective killing of hepatitis B envelope antigen-specific B cells by class I-restricted, exogenous antigen-specific T lymphocytes.

Specific B lymphocytes can act as very efficient antigen-presenting cells. They bind antigen with high affinity via their immunoglobulin receptors, process it through the class II major histocompatibility complex (MHC) pathway, and present its fragments to class II-restricted T lymphocytes. In general, exogenous antigens and noninfectious viral particles enter the class II pathway and are selectively associated with class II MHC molecules. The presentation of an exogenous antigen in association with class I molecules has been reported for only a few antigens, including the hepatitis B envelope antigen (HBenvAg). Here we demonstrate that antigen-specific B cells can efficiently deliver HBenvAg to the class I pathway, presenting its fragments to class I-restricted cytotoxic T lymphocytes (CTLs) which kill the specific B cells. This could represent a mechanism of suppression of neutralizing anti-hepatitis B virus (HBV) antibody response, a phenomenon that accompanies the development of the chronic HBV-carrier state.

Antibodies, Monoclonal↗
PubMed1990

Liver-derived T cell clones in autoimmune chronic active hepatitis: accessory cell function of hepatocytes expressing class II major histocompatibility complex molecules.

Thirty T cell clones were generated from T cell blasts, infiltrating the liver of autoimmune chronic active hepatitis (CAH) patients, stimulated with autologous hepatocytes expressing class II major histocompatibility complex (MHC) molecules and interleukin 2 (IL2). Sixteen clones were CD4+ and 14 were CD8+; all were CD25+ and WT31+, revealing that all cell lines expressed the alpha/beta chains of T cell receptor. Five CD4+ and 4 CD8+ T clones proliferated in response to hepatocytes expressing both class I and class II antigens. The hepatocyte recognition was MHC restricted because only class II MHC-matched hepatocytes were able to stimulate the CD4+ T clones, while only class I-matched hepatocytes stimulated CD8+ T clones, and because MoAbs to monomorphic determinants of class II antigens or to class I antigens appeared to block the response of the CD4+ and CD8+ T clones, respectively. These findings, together with the observation that autologous irradiated peripheral blood mononuclear cells (iPBMC) were unable to stimulate the clones, indicate that the response of these clones was directed to a liver membrane antigen in association with class II or class I MHC molecules on the surface of the hepatocytes. All the CD8+ T clones and 5 CD4+ T clones expressed high cytotoxic activity in a lectin-dependent cell-mediated cytotoxicity assay; 10 CD8+ and 3 CD4+ T clones also showed natural killer (NK)-like function. The cytolytic machinery was also present in those clones (both CD8 and CD4) recognizing the HLA-matched hepatocytes. All liver-derived T clones were able to produce high amounts of interferon (IFN)-gamma, as well as being capable of secreting IL2, following PHA stimulation.

Antibody Formation↗
PubMed1989

Recognition of hepatitis B virus envelope proteins by liver-infiltrating T lymphocytes in chronic HBV infection.

The Ag specificity and cytotoxic function of human T cell clones, generated from lymphocytes infiltrating the liver of a chronic hepatitis B patient, were studied. Both class I- and class II-restricted T clones specifically proliferated to hepatitis B virus envelope proteins, but not to hepatitis B core Ag. The fine specificity of T cells was studied by using rAg having different composition in relation to HBV-envelope proteins or synthetic peptides of preS regions. The antigenic determinant recognized by T cell clones mapped to the preS2 region based on the response to r(preS1+preS2+S) and to r(preS2+S) and the failure to respond to S or preS1 alone. More precise epitope mapping was based on synthetic preS2 peptides 120-150 or 120-134, which stimulated both class I- and class II-restricted T clones, whereas preS2 153-171 or preS1 1-110 peptides did not; thus, the preS2 120-134 appears to contain both the residues binding to class I molecules and the residues binding to class II molecules. Moreover, strong and specific cytotoxic responses of these clones were observed only when HLA-matched EBV-lines, used as target cells, were previously sensitized with r(preS1+preS2+S) or preS2 peptides, which were shown to stimulate the clones. Thus, a preS2 epitope can represent a target Ag for liver-infiltrating T cells, which could kill the hepatocytes expressing the Ag plus the appropriate MHC molecule.

Adult↗
PubMed1988

Increased number of CD4 cells able to bind to natural killer cell targets in the peripheral blood of AIDS related complex patients.

CD4 cells forming conjugates with natural killer target cells (K562 cells) were measured in the peripheral blood of anti-HIV antibody positive AIDS related complex (ARC) patients and in three control groups (asymptomatic individuals at risk, normal healthy people and patients with acute hepatitis B). These CD4 cells, which are unable to kill K562 cells, were significantly increased in ARC patients as compared to the control groups. Our data indicate that classical CD4 cells are partially replaced, in ARC patients, by a population of natural killer-target binding granular CD4 lymphocytes, and suggest that the functional abnormalities of helper T cells in these patients may be in part a consequence of the relative predominance of these non IL-2 and BCGF producing cells within the circulating CD4 population.

AIDS-Related Complex↗
PubMed1987

A calf thymus acid lysate improves clinical symptoms and T-cell defects in the early stages of HIV infection: second report.

Thymomodulin is a calf thymus acid lysate capable of inducing T lymphocyte maturation. Fifteen patients with HIV infection at different stages according to the Walter Reed classification were treated with 60 mg/day of thymomodulin syrup for more than 50 days. Two WR6B subjects had clinical and immunological parameters unchanged and died, while the patient suffering from Kaposi's sarcoma presented an evident clinical and laboratory improvement with remission of the neoplasia. The other 12 patients ranging from WR2 to WR5B showed an improvement of clinical symptoms after thymomodulin therapy accompanied by the normalization of CD4/CD8 ratio (P less than 0.001). This helpers/suppressors increase was due to a significant increase of CD4 cells (P less than 0.01) and also to a decrease of the CD8 lymphocytes (P less than 0.05). Thymomodulin administration did not cause an enhancement of the urinary levels of neopterin, a marker of T-cell activation.

Acquired Immunodeficiency Syndrome↗
PubMed1987

In vitro induction of HBsAg-specific CD8 CD11 human suppressor T cells.

Anti-hepatitis B surface (HBs) antibodies have been induced in vitro by human peripheral blood mononuclear cells (PBMC) from individuals immunized with hepatitis B surface antigen (HBsAg). Anti-HBs antibody production is antigen-specific, T-cell dependent, class II MHC-restricted and requires de novo synthesis. Furthermore, HBsAg-specific CD8 suppressor cells can also be induced in vitro after challenge with high antigen doses. Antigen presenting cells (APC) are required for the induction of suppression. These suppressor cells are antigen-specific since they do not suppress the antibody response to tetanus toxoid. Antigen-specific suppression is inhibited by cytotoxic treatment of CD8 CD11 cells with OKM1 monoclonal antibody (MoAb) and complement, suggesting that these suppressor CD8 cells may represent granular lymphocytes. Addition to cultures of high concentrations of a recombinant human IL-2 dose not affect suppression, ruling out the adsorption of IL-2 by suppressor cells as a possible mechanism for suppression.

Cells, Cultured↗