Expanding the functional CD8+ T cell repertoire reduces HSV-1 reactivation from latency in sensory ganglia

Following corneal infection, herpes simplex virus (HSV)-1 establishes latency in sensory neurons of the trigeminal ganglia (TG). In humans, spontaneous and recurrent reactivation of HSV-1 from latency has the potential to cause lesions on the gums (stomatitis), lips (cold sores, fever blisters), cornea (stromal keratitis), and brain (encephalitis). Latently infected neurons were once thought be largely ignored by the host immune system. Existing evidence shows that not only do HSV-specific CD8 T cells recognize latently infected neurons; they actively maintain viral latency using proinflammatory cytokines and lytic granules containing granzymes. The premise of this study further characterized the nature of the CD8 T cell response. Previous studies displayed that in the C57BL/6 mouse; CD8 T cells infiltrate the TG and become situated in direct apposition to infected neurons. It was known that 50 % of the CD8 T cells recognized the immunodominant epitope on glycoprotein B (gB) while the specificities of the remaining CD8 T cells were undefined. In this study, we observed that the non-gB CD8 T cell repertoire was confined to 18 epitopes on 11 viral proteins. During acute infection, these cells, similar to gB498-505-specific CD8 T cells, readily produce cytokines and release lytic granules upon stimulation. Conversely, during latency, even though these cells remain in the TG, they lose the ability to produce cytokines and release lytic granules upon stimulation suggesting functional compromise, unlike gB498-505-specific CD8 T cells. We show that the immunosuppressive cytokine, IL-10, preferentially suppresses the non-gB498-505-specific CD8 T cell population. Upon administration of an antibody against the IL-10 receptor, we see a dramatic increase in functional non-gB498-505-specific CD8 T cells without apparent effect in the gB498-505-specific CD8 T cell population. This increase in functional CD8 T cells leads to a 50% reduction in viral reactivation from latency suggesting the possibility of anti-IL10R as a treatment of recurrent reactivation of HSV-1 from latency

DIPL 6116 The Palestinian-Israeli Negotiations and Peace Process

Prerequisite: DIPL 6104/4183 Art and Science of International Negotiation or permission of instructor. The Palestinian-Israeli conflict is generally thought to be intractable. Much journalistic and even scholarly work tends to be partisan, while contributing little to our understanding of how this conflict can be resolved. In fact, there is a significant history of attempts to transform this conflict into coexistence, some of it more and some of it less successful. The instructor will build on his significant field research into the open and secret negotiations between Israel and the PLO, as well as the long history of Arab­ Zionist encounters. Participants will the course by applying lessons learned to other major, seemingly intractable conflicts. A major component of the class will be the simultaneous conduct of actual negotiations by the participants, who will join one of four delegations: a Palestinian or an Israeli negotiation delegation, negotiating either interim or permanent issues. For Summer 2003, the course will be taught as an intensive, one week executive format. Beyond learning the significant history, diplomacy and negotiation efforts, participants will gain insight by actually joining either an Israeli or Palestinian delegation and negotiating

DIPL 1001 Games of International Relations

In this concentrated module, you will 1. become aware of concepts from game theory and 2. learn how to apply them to historical and current events in international relations, including international conflicts and international negotiations 3. gain knowledge of this complex topic in a way that is enjoyable, retainable and useful for your further study at the Whitehead School. Class discussion will be emphasized, as well as historical knowledge and analytical thinking. A significant, but short writing assignment will be used to assess your learning. There will be a series of critical readings, but no single textbook. The level of the reading is advanced, but you are expected to \u27stretch\u27 in order to grasp what is being discussed, and in-class discussions will be used to clarify and apply these concepts. Failures to do the readings, tum in assignments on time or to properly cite sources (plagiarism) are grounds for a grade of F, and possible expulsion from the Whitehead School

The influence of depression-PTSD comorbidity on health-related quality of life in treatment-seeking veterans

Objective: Posttraumatic stress disorder (PTSD) and depression substantially impair healthrelated quality of life (HRQOL) for many Canadian Armed Forces (CAF) veterans. Although PTSD and depression are highly comorbid, little is known about whether the disorders may interact in their association with HRQOL. We sought to investigate whether depressive symptoms modify the relation between PTSD and HRQOL in treatment-seeking veterans. Method: We accessed the clinical data of 545 CAF veterans aged 18 to 65 years who were seeking treatment at a specialized clinic in London, Ontario. We used hierarchical linear regression to assess the additive and multiplicative relations between depression and PTSD symptoms on HRQOL, controlling for age and alcohol/substance abuse. Simple slopes were examined to probe significant interactions. Results: Probable PTSD and major depression were present in 77.4% and 85.3% of the sample, respectively, and 73.0% of the sample presented with probable PTSD-depression comorbidity. Depression symptoms significantly modified the relation between PTSD symptoms and overall mental HRQOL (β = 0.12,