SUMMARYAbnormal CD4/CD8 ratios and T-cell function have previously been shown in patients with B-chronic lymphocytic leukaemia (B-CLL). We have demonstrated that CD4 1 T cells containing both serine esterase and perforin (PF) are increased in the blood of these patients. Using flow cytometry, we have shown that the CD4 1 PF 1 cells were CD57 1 but lacked expression of CD28, suggesting a mature population. The same phenotype in CD8 1 T cells is characteristic of mature cytotoxic T cells. However, in contrast to the CD8 1 T cells, the CD4 1 T cells were more frequently CD45RO positive than CD45RA positive, indicating prior antigen experience. In contrast, this population lacked expression of either CD69 or HLA-DR, arguing that they were not activated or that they are an abnormal population of T cells. Their constitutive cytokine levels showed them mainly to contain IL4 and not IFNg, suggesting a Th2 phenotype. The role of the CD4 1 PF 1 T-cell population is at present uncertain. However, this potentially cytotoxic T-cell population could contribute both to enhancing survival of the B-CLL tumour cells through production of IL4, and to the immunodeficient state frequently seen in patients with this tumour, independent of drug treatment.

This research identified psychosocial factors associated with post-traumatic stress and health anxiety following a venous thrombotic embolism. In all, 158 participants, largely registered with a venous thrombotic embolism information website (Lifeblood: The Thrombosis Charity), completed an online survey. Post-traumatic symptom scores were linked to health threat, and not moderated by perceived control over risk for further venous thrombotic embolism. Health anxiety was associated with continuing symptoms and a negative emotional response to the venous thrombotic embolism. There is a need to intervene to reduce both short- and long-term distress in this population, ideally using a stepped-care model.

There are shared objectives between psychiatry and palliative care; however, currently, co-involvement on treatment teams is quite limited. Future research is needed to identify ways to facilitate the interface of palliative care and psychiatry.

Little has been known about Tlr13 (Toll-like receptor 13), a novel member of the Toll-like receptor family. To elucidate the molecular basis of murine Tlr13 gene expression, the activity of the Tlr13 gene promoter was characterized. Reporter gene analysis and electrophoretic mobility shift assays demonstrated that Tlr13 gene transcription was regulated through three cis-acting elements that interacted with the Ets2, Sp1, and PU.1 transcription factors. Furthermore, our work suggests that these transcription factors may cooperate, culminating in maximal transcription of the Tlr13 gene. In contrast, NF-B appeared to act as an inhibitor of Tlr13 transcription. Overexpression of Ets2 caused a strong increase in the transcriptional activity of the Tlr13 promoter; however, overexpression of NF-B p65 dramatically inhibited it. Additionally, interferon-␤ is capable of acting Tlr13 transcription, but the activated signaling of lipopolysaccharide/TLR4 and peptidoglycan/TLR2 strongly inhibited the Tlr13 gene promoter. Thus, these findings reveal the mechanism of Tlr13 gene regulation, thereby providing insight into the function of Tlr13 in the immune response to pathogen.Upon infection, microorganisms are first recognized by cells of the host innate immune system, such as macrophages and dendritic cells, as well as mucosal epithelial cells (1-6). Recognition of pathogens is primarily mediated by a set of germ lineencoded molecules on innate immune cells that are referred to as pattern recognition receptors (7,8). These pattern recognition receptors are expressed as either membrane-bound or soluble proteins that recognize invariant molecular structures from the pathogen called pathogen-associated molecular patterns (7,8).Recent studies on the recognition of microbial pathogenassociated molecular patterns have highlighted the vital role of one group of pattern recognition receptors, the Toll-like receptors (TLRs) 2 (9, 10). It is already clear that TLRs play a crucial role in the recognition of "molecular signatures" produced by infecting microbes to engage differential signaling pathways (11,12). Signaling through TLRs activates various transcription factors, such as nuclear factor-B (NF-B), activating protein-1 (AP-1), and interferon regulatory factors to induce an immunological response (3, 11).Tlr13 is a novel and poorly characterized member of the Tolllike receptor family (3, 13). Although the elucidation of the function of Tlr13 depends mainly on the identification of its natural ligand, its transcriptional regulation also provide some clues. For example, which type of cells expresses Tlr13? Which transcription factors control Tlr13 expression? How do different pathogen-associated molecular patterns from different pathogens regulate Tlr13 expression? This information will perhaps help us understand not only how this novel TLR responds to different infections but also which pathogens might be recognized by Tlr13 to activate the innate immune response. Recently, Aderem et al. (14) reported that Tlr13 belongs to the Tlr1...

Posttransplant lymphoproliferative disorders (PTLDs) represent life-threatening complications of bone marrow and solid organ transplantation (SOTx). These are B-cell malignancies triggered by Epstein-Barr Virus (EBV) infection in chronically immunosuppressedRestoration of protective anti-Epstein-Barr Virus (anti-EBV) T-cell immunity by adoptive transfer of ex vivo expanded EBV-specific cytotoxic T lymphocytes (CTLs) has been shown to be a safe and effective approach to prevent or treat posttransplant lymphoproliferative disorders (PTLDs) in bone marrow transplant recipients (1-3). Standard published protocols emphasize the effectiveness of using autologous lymphoblastoid cell lines (LCLs) as stimulator cells in boosting memory immune responses to EBV in vitro (2,3). However this same approach has not proven effective in priming naïve anti-EBV T cells in vitro (4,5). As EBV − SOTx recipients are at high risk of developing PTLD, we have been interested in establishing protocols to generate EBV-specific CTLs from these individuals. Studies performed by other groups, and in our laboratory, have recently established the key role of using dendritic cells (DCs) as antigen-presenting cells in activating naïve T cells against EBV epitopes (6,7). In the current study we wanted to assess and compare the ability of DCs loaded with necrotic/apoptotic LCLs in cross-priming autologous naïve EBV-reactive T cells vs. boosting memory T cells, and to further characterize the quality of the resulting immune responses.The CTL lines were evaluated by flow cytometry analyses with MHC Class I/peptide tetramers and mAbs to detect memory/activation markers, ELISPOT analysis for IFN-c production, and in cytotoxicity tests. Results indicate that in our system, in vitro cross-priming promotes both activated poly-epitope viral-specific CD8+ CTLs and Th1-type CD4+ T-cell responses in EBV − donors. The polarized Type 1 pattern of cytokine expression induced by DCs fed with apoptotic/necrotic LCLs correlated with the ability of T cells to mediate cytotoxicity against autologous LCLs, which was further enhanced by addition of rhIL-12 in the first round of in vitro stimulation. These results support the prospective development of DC-based cellular immunotherapy for EBV − SOTx patients at high risk of developing PTLD or patients with refractory PTLD. Materials and Methods Human subjectsSeven immunocompetent adult volunteers were recruited in this study following informed consent under IRB-approved protocol. Peripheral blood mononuclear cells (PBMCs) were isolated from heparinized blood (8), while sera served as material for determination of EBV status. 1369