A repetitive sequence of Epstein-Barr virus nuclear antigen 6 comprises overlapping T cell epitopes which induce HLA-DR-restricted CD4(+) T lymphocytes

Most human adults carry the Epstein-Barr virus (EBV) and develop immunological memory against the structural and the virus-encoded cellular proteins. The EBV nuclear antigen 6 (EBNA6) elicits cytotoxic T cell responses and it also maintains a persistent antibody response. The majority of sera from EBV-seropositive individuals reacts with a synthetic peptide, p63, comprising 21 amino acids of a repetitive region of EBNA6. CD4(+) T lymphocytes, with specificity for p63, could be recalled from the T cell repertoire of EBV carriers that expressed certain HLA-DR allotypes which were identified as good binders of p63 by an in vitro flow cytometric assay. Analysis of the HLA-DR/p63 interaction by molecular mechanics calculations indicated the presence of multiple overlapping epitopes which were predicted to bind in a HLA-DRB1 allo- and subtype-specific manner. Specific activation of p63-selected long-term CD4(+) T cell cultures resulted in a proliferative response, in the production of IL-2 and in the secretion of high levels of tumor necrosis factor as measured by bioassays. Proliferation and cytokine production of p63-specific T cells could be induced by p63-loaded HLA-DR-matched antigen-presenting cells and by B cells co-expressing relevant HLA-DR molecules and EBNA6. Our results show that peptides of an EBNA6 repeat region induce CD4(+) T cells which can react with EBNA6-carrying cells in many individuals. We suggest that these T(h) cells may be important in conditioning dendritic cells for initiation potent virus-specific immune responses, provide help for EBV-specific B cells, drive IgG isotype switch and support the sustained effector function of memory cytotoxic T lymphocytes

Postnatal lung function after prenatal steroid treatment in sheep: Effect of gender

The effect of fetal gender on postnatal lung function and response to prenatal steroid exposure were examined retrospectively in a group of 115 preterm lambs. Fetuses received a single intramuscular injection of 0.5 mg/kg betamethasone alone or in conjunction with L-thyroxine 48 h before delivery at 128-d gestational age. Control animals received an equivalent volume of saline. After delivery, respiratory mechanics and blood gas parameters were recorded for 40 min. Deflation pressure volume curves were constructed in excised lungs. Right upper lobes from a randomly selected subgroup of control animals were examined morphometrically. Control (saline-treated) females were able to be ventilated at lower ventilatory pressures with equivalent tidal volumes and more efficient gas exchange. There were no gender differences in compliance, conductance, or excised lung volumes for saline-treated animals. More efficient gas exchange in females could not be explained by thinner alveolar septa or greater alveolar surface area. After hormone treatment, both males and females exhibited significant improvements in respiratory mechanics, gas exchange, and an increase in alveolar surfactant concentration. However, females exhibited a significantly greater improvement than males for compliance, conductance, excised lung volume, and arterial oxygen partial pressure. These data provide a comprehensive description of gender differences in postnatal lung function and response to steroid treatment in preterm animals, and support clinical findings of sexual dimorphism