Neuropilin-1 Regulates the Secondary CD8 T Cell Response to Virus Infection.

Neuropilin-1 (Nrp1) plays important roles in axonal guidance in neurons and in the growth of new blood vessels. There is also a growing appreciation for roles played by neuropilin-1 in the immune response. This molecule is important for the function of regulatory T cells; however, roles in other T cell populations have not been identified. Here, we show that neuropilin-1 is expressed during the peak of the antiviral CD8 T cell response during murine gammaherpesvirus infection. Using a conditional knockout model, we deleted Nrp1 either before infection or after CD8 T cell memory had been established. We found that deletion of Nrp1 skewed the acute CD8 T cell response toward a memory precursor-like phenotype; however, the ensuing resting memory response was similar regardless of Nrp1 expression. Interestingly, Nrp1 deletion had differing effects on the recall response depending on the timing of deletion. When deleted before infection, Nrp1 deficiency inhibited the secondary response. Deletion just prior to reexposure to virus led to an enhanced secondary response. Interestingly, these effects were observed only in mice infected with a persistent strain of murine gammaherpesvirus and not with a nonpersistent mutant strain. These data highlight a multifaceted role for neuropilin-1 in memory CD8 T cell differentiation, dependent upon the stage of the T cell response and characteristics of the infectious agent. Several therapeutic anticancer therapies focus on inhibition of Nrp1 to restrict tumor growth, and so knowledge of how Nrp1 blockade may affect the CD8 T cell response will provide a better understanding of treatment consequences.IMPORTANCE CD8 T cell responses are critical to control both virus infections and tumors. The ability of these cells to persist for long periods of time can result in lifelong immunity, as relatively small populations of cells can expand rapidly to counter reexposure to the same insult. Understanding the molecules necessary for this rapid secondary expansion is critical if we are to develop therapies that can provide lifelong protection. This report shows an important and complex role for the molecule neuropilin-1 in the secondary response. Several cancer therapies targeting neuropilin-1 are in development, and this work will lead to better understanding of the effect these therapies could have upon the protective CD8 T cell response.

The prevalence of depression and the accuracy of depression screening tools in migraine patients.

OBJECTIVES: Migraine and depression are common comorbid conditions. The purpose of this study was to assess how well the Patient Health Questionnaire (PHQ-9) and the Hospital Anxiety and Depression Scale (HADS) perform as depression screening tools in patients with migraine. METHODS: Three hundred consecutive migraine patients were recruited from a large headache center. The PHQ-9 and HADS were self-administered and validated against the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-IV, a gold standard for the diagnosis of depression. Sensitivity, specificity, positive predictive value, negative predictive value and receiver-operator characteristic curves were calculated for the PHQ-9 and HADS. RESULTS: At the traditional cut-point of 10, the PHQ-9 demonstrated 82.0% sensitivity and 79.9% specificity. At a cut-point of 8, the HADS demonstrated 86.5% sensitivity and specificity. The PHQ-9 algorithm performed poorly (53.8% sensitivity, 94.9% specificity). The point prevalence of depression in this study was 25.0% (95% CI 19.0-31.0), and 17.0% of patients had untreated depression. CONCLUSIONS: In this study, the PHQ-9 and HADS performed well in migraine patients attending a headache clinic, but optimal cut-points to screen for depression vary depending on the goals of the assessment. Also, migraine patients attending a headache clinic have a high prevalence of depression and many are inadequately treated. Future studies are needed to confirm these findings and to evaluate the impact of depression screening.