Cutting edge: precursor frequency affects the helper dependence of cytotoxic T cells.

Generation of CTL immunity often depends on the availability of CD4 T cell help. In this report, we show that CTL responses induced by cross-priming can be converted from CD4-dependent to CD4-independent by increasing the frequency of CTL precursors. In the absence of CD4 T cells, high numbers of CTL precursors were able to expand in number and become effector CTL. The ability of high frequencies of CD8 T cells to override help was not due to their ability to signal CD40 via expression of CD154. These findings suggest that when precursor frequencies are high, priming of CD8 T cell responses may not require CD4 T cell help.     

Clade-specific morphological diversification and adaptive radiation in Hawaiian songbirds.

The Hawaiian honeycreepers are a dramatic example of adaptive radiation but contrast with the four other songbird lineages that successfully colonized the Hawaiian archipelago and failed to undergo similar diversification. To explore the processes that produced the diversity dichotomy in this insular fauna, we compared clade age and morphological diversity between the speciose honeycreepers and the comparatively depauperate Hawaiian thrushes. Mitochondrial-DNA-based genetic distances between these Hawaiian clades and their continental sister taxa indicate that the ancestral thrush colonized the Hawaiian Islands as early as the common ancestor of the honeycreepers. This similar timing of colonization indicates that the marked difference in diversity between the Hawaiian honeycreeper and thrush clades is unlikely to result from differences in these clades' tenures within the archipelago. If time cannot explain the contrasting diversities of these taxa, then an intrinsic, clade-specific trait may have fostered the honeycreeper radiation. As the honeycreepers have diversified most dramatically in morphological characters related to resource utilization, we used principal components analyses of bill characters to compare the magnitudes of morphological variation in the ancestral clades from which the Hawaiian honeycreeper and thrush lineages are derived, the Carduelini and Turdinae respectively. Although the Carduelini share a more recent common ancestor and have a lower species diversity than the Turdinae, these finch-like relatives of the honeycreepers exhibit significantly greater variation in bill morphology than do the continental relatives of the Hawaiian thrushes. The higher magnitude of morphological variation in the non-Hawaiian Carduelini suggests that the honeycreepers fall within a clade exhibiting a generally high evolutionary flexibility in bill morphology. Accordingly, although the magnitude of bill variation among the honeycreepers is similar to that of the entire passerine radiation, this dramatic morphological radiation represents an extreme manifestation of a general clade-specific ability to evolve novel morphologies.     

Induction of SerpinB2 and Th1/Th2 Modulation by SerpinB2 during Lentiviral Infections In Vivo

SerpinB2, also known as plasminogen activator inhibitor type 2, is a major product of activated monocytes/macrophages and is often strongly induced during infection and inflammation; however, its physiological function remains somewhat elusive. Herein we show that SerpinB2 is induced in peripheral blood mononuclear cells following infection of pigtail macaques with CCR5-utilizing (macrophage-tropic) SIV_mac239, but not the rapidly pathogenic CXCR4-utilizing (T cell-tropic) SHIV_mn229. To investigate the role of SerpinB2 in lentiviral infections, SerpinB2^−/− mice were infected with EcoHIV, a chimeric HIV in which HIV gp120 has been replaced with gp80 from ecotropic murine leukemia virus. EcoHIV infected SerpinB2^−/− mice produced significantly lower anti-gag IgG1 antibody titres than infected SerpinB2^+/+ mice, and showed slightly delayed clearance of EcoHIV. Analyses of published microarray studies showed significantly higher levels of SerpinB2 mRNA in monocytes from HIV-1 infected patients when compared with uninfected controls, as well as a significant negative correlation between SerpinB2 and T-bet mRNA levels in peripheral blood mononuclear cells. These data illustrate that SerpinB2 can be induced by lentiviral infection in vivo and support the emerging notion that a physiological role of SerpinB2 is modulation of Th1/Th2 responses.     

Demonstrating the Potential for Dynamic Auditory Stimulation to Contribute to Motion Sickness

Auditory cues can create the illusion of self-motion (vection) in the absence of visual or physical stimulation. The present study aimed to determine whether auditory cues alone can also elicit motion sickness and how auditory cues contribute to motion sickness when added to visual motion stimuli. Twenty participants were seated in front of a curved projection display and were exposed to a virtual scene that constantly rotated around the participant''s vertical axis. The virtual scene contained either visual-only, auditory-only, or a combination of corresponding visual and auditory cues. All participants performed all three conditions in a counterbalanced order. Participants tilted their heads alternately towards the right or left shoulder in all conditions during stimulus exposure in order to create pseudo-Coriolis effects and to maximize the likelihood for motion sickness. Measurements of motion sickness (onset, severity), vection (latency, strength, duration), and postural steadiness (center of pressure) were recorded. Results showed that adding auditory cues to the visual stimuli did not, on average, affect motion sickness and postural steadiness, but it did reduce vection onset times and increased vection strength compared to pure visual or pure auditory stimulation. Eighteen of the 20 participants reported at least slight motion sickness in the two conditions including visual stimuli. More interestingly, six participants also reported slight motion sickness during pure auditory stimulation and two of the six participants stopped the pure auditory test session due to motion sickness. The present study is the first to demonstrate that motion sickness may be caused by pure auditory stimulation, which we refer to as “auditorily induced motion sickness”.