Subject index, Volume 70

Subject Index

Subject index, Volume 70     

Recruitment of effector lymphocytes by initiator lymphocytes: role of a trypsin-sensitive membrane component

In earlier studies we found that initiator T lymphocytes sensitized in vitro against fibroblasts were able to recruit immunospecific effector T lymphocytes in vivo in syngeneic mice. In the present study, to investigate the possible function in effector cell recruitmentof sensitizing antigens passively adsorbed onto the initiator cell membrane, we treated the initiator lymphocytes with trypsin. We found that trypsin inhibited recruitment. However, the initiator cells spontaneously recovered their recruiting ability after incubation in vitro for 4 h in the absence of contact with sensitizing antigens. Recovery could be blocked by cycloheximide. Hence, it appears that recruitment depends on the intrinsic metabolic function of the initiator lymphocytes and is not due merely to passively-adsorbed antigen carried over into the recipient mouse.     

Time limited immunomodulatory functions of transplanted neural precursor cells

Fetal neural stem/precursor cells (NPCs) possess powerful immunomodulatory properties which enable them to protect the brain from immune‐mediated injury. A major issue in developing neural stem/precursor cell (NPC) therapy for chronic neuroinflammatory disorders such as multiple sclerosis is whether cells maintain their immune‐regulatory properties for prolonged periods of time. Therefore, we studied time‐associated changes in NPC immunomodulatory properties. We examined whether intracerebrally‐transplanted NPCs are able to inhibit early versus delayed induction of autoimmune brain inflammation and whether allogeneic NPC grafts continuously inhibit host rejection responses. In two experimental designs, intraventricular fetal NPC grafts attenuated clinically and pathologically brain inflammation during early EAE relapse but failed to inhibit the disease relapse if induced at a delayed time point. In correlation, long‐term cultured neural precursors lost their capacity to inhibit immune cell proliferation in vitro. Loss of NPC immune functions was associated with transition into a quiescent undifferentiated state. Also, allogeneic fetal NPC grafts elicited a strong immune reaction of T cell and microglial infiltration and were rejected from the host brain. We conclude that long‐term functional changes in transplanted neural precursor cells lead to loss of their therapeutic immune‐regulatory properties, and render allogeneic grafts vulnerable to immunologic rejection. Thus, the immunomodulatory effects of neural precursor cell transplantation are limited in time. © 2012 Wiley Periodicals, Inc.     

Severe factor X deficiency in three unrelated Palestinian patients is caused by homozygosity for the mutation c302delG-correlation with thrombin generation and thromboelastometry

Factor X (FX) is one of the vitamin K-dependent serine proteases, which forms the prothrombinase complex converting prothrombin into thrombin. To search for mutations in F10 gene giving rise to severe FX deficiency and to study the contribution of thrombin generation and thromboelastometry as a tool for evaluation of hemostasis. Mutations in the F10 gene were sought by direct sequencing of all the eight exons and intron/exon boundaries. Thrombin generation and thromboelastometry were performed. Three unrelated Palestinian patients had undetectable FX level (<1?U/dl). All patients were found to be homozygous for c302delG, a new frameshift mutation in the F10 gene causing a stop codon at amino acid 73. The mutant allele was not detected among 152 Palestinians analyzed. Thrombin generation was examined in one of the patients 4 days after fresh frozen plasma was applied, when his FX level was 2?U/dl. Minute thrombin generation was observed, as compared to normal thrombin generation in heterozygotes for the mutation and a healthy control. Thromboelastometry revealed prolonged lag phase when patient's platelet-poor plasma and platelet-rich plasma were tested, with a slightly decreased initial clot formation rate, as compared to carriers' and control sample. Genetic analysis disclosed a unique mutation causing a severe phenotype. Thrombin generation assay may serve as a quick tool for confirming severe deficiency until the specific mutation is identified. Thrombin generation can also serve for monitoring and optimizing treatment. The correlation of thromboelastometry assay and severe FX deficiency is less striking.