Inducible deletion of CD28 prior to secondary nippostrongylus brasiliensis infection impairs worm expulsion and recall of protective memory CD4 (+) T cell responses

IL-13 driven Th2 immunity is indispensable for host protection against infection with the gastrointestinal nematode Nippostronglus brasiliensis. Disruption of CD28 mediated costimulation impairs development of adequate Th2 immunity, showing an importance for CD28 during the initiation of an immune response against this pathogen. In this study, we used global CD28−/− mice and a recently established mouse model that allows for inducible deletion of the cd28 gene by oral administration of tamoxifen (CD28−/loxCre+/−+TM) to resolve the controversy surrounding the requirement of CD28 costimulation for recall of protective memory responses against pathogenic infections. Following primary infection with N. brasiliensis, CD28−/− mice had delayed expulsion of adult worms in the small intestine compared to wild-type C57BL/6 mice that cleared the infection by day 9 post-infection. Delayed expulsion was associated with reduced production of IL-13 and reduced serum levels of antigen specific IgG1 and total IgE. Interestingly, abrogation of CD28 costimulation in CD28−/loxCre+/− mice by oral administration of tamoxifen prior to secondary infection with N. brasiliensis resulted in impaired worm expulsion, similarly to infected CD28−/− mice. This was associated with reduced production of the Th2 cytokines IL-13 and IL-4, diminished serum titres of antigen specific IgG1 and total IgE and a reduced CXCR5+ TFH cell population. Furthermore, total number of CD4+ T cells and B220+ B cells secreting Th1 and Th2 cytokines were significantly reduced in CD28−/− mice and tamoxifen treated CD28−/loxCre+/− mice compared to C57BL/6 mice. Importantly, interfering with CD28 costimulatory signalling before re-infection impaired the recruitment and/or expansion of central and effector memory CD4+ T cells and follicular B cells to the draining lymph node of tamoxifen treated CD28−/loxCre+/− mice. Therefore, it can be concluded that CD28 costimulation is essential for conferring host protection during secondary N. brasiliensis infection

T-cell Subset Regulation in Atopy

Presentation of processed allergen by antigen-presenting cells to T-helper (Th) lymphocytes, which is influenced costimulatory signals, cytokines, chemokines, and regulatory T cells (Tregs), determines the development of different types of T-cell immunity. The discovery of Tregs revolutionized the primary concepts of immune regulation interpreted within the framework of a binary Th1/Th2 paradigm. Tregs play a central role in the maintenance of peripheral homeostasis, the establishment of controlled immune responses, and the inhibition of allergen-specific effector cells. Recently, some other T-cell subsets appeared, including Th17 and Th9 cells, which control local tissue inflammation through upregulation of proinflammatory cytokines and chemokines. This review aims to discuss our understanding of the T-cell subset reciprocal interaction in atopy

Species Interactions during Diversification and Community Assembly in an Island Radiation of Shrews

Closely related, ecologically similar species often have adjacent distributions, suggesting competitive exclusion may contribute to the structure of some natural communities. In systems such as island archipelagos, where speciation is often tightly associated with dispersal over oceanic barriers, competitive exclusion may prevent population establishment following inter-island dispersal and subsequent cladogenesis.) species in the Philippines are the result of competitive exclusion preventing secondary invasion of occupied islands. We first compare ecological niche models between two widespread, allopatric species and find statistical support for their ecological similarity, implying that competition for habitat between these species is possible. We then examine dispersion patterns among sympatric species and find some signal for overdispersion of body size, but not for phylogenetic branch length. Finally, we simulate the process of inter-island colonization under a stochastic model of dispersal lacking ecological forces. Results are dependent on the geographic scope and colonization probability employed. However, some combinations suggest that the number of inter-island dispersal events necessary to populate the archipelago may be much higher than the minimum number of colonization events necessary to explain current estimates of species richness and phylogenetic relationships. If our model is appropriate, these results imply that alternative factors, such as competitive exclusion, may have influenced the process of inter-island colonization and subsequent cladogenesis.We interpret the combined results as providing tenuous evidence that similarity in body size may prevent co-occurrence in Philippine shrews and that competitive exclusion among ecologically similar species, rather than an inability to disperse among islands, may have limited diversification in this group, and, possibly other clades endemic to island archipelagos

Resource heterogeneity and community structure: A case study in Heliconia imbricata Phytotelmata

Complex or non-additive differences in the distribution and abundance of arthropod species inhabiting the water-filled bracts of Heliconia imbricata can be created by simple manipulations of resource levels. The primary resources for these assemblages are the corollas of the flowers that accumulate in the bracts. Removing or adding corollas to individual bracts changes the pattern in the abundance of arthropod species within each bract such that bracts with different treatments ultimately differ in composition and numerical associations among species. These results suggest that direct and indirect resource-mediated factors can structure or significantly affect the distribution and abundance of species in these and perhaps other assemblages. Thus, in natural communities, if resources are heterogeneous among patches (such as among the bracts in this study) structure in a given patch may be a function of the resource level of that patch and can differ significantly from neighboring patches that provide different resource levels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47788/1/442_2004_Article_BF00665591.pd

IL-4Ralpha-associated antigen processing by B cells promotes immunity in Nippostrongylus brasiliensis infection.

In this study, B cell function in protective T(H)2 immunity against N. brasiliensis infection was investigated. Protection against secondary infection depended on IL-4Ralpha and IL-13; but not IL-4. Protection did not associate with parasite specific antibody responses. Re-infection of B cell-specific IL-4Ralpha(-)/(-) mice resulted in increased worm burdens compared to control mice, despite their equivalent capacity to control primary infection. Impaired protection correlated with reduced lymphocyte IL-13 production and B cell MHC class II and CD86 surface expression. Adoptive transfer of in vivo N. brasiliensis primed IL-4Ralpha expressing B cells into naive BALB/c mice, but not IL-4Ralpha or IL-13 deficient B cells, conferred protection against primary N. brasiliensis infection. This protection required MHC class II compatibility on B cells suggesting cognate interactions by B cells with CD4(+) T cells were important to co-ordinate immunity. Furthermore, the rapid nature of these protective effects by B cells suggested non-BCR mediated mechanisms, such as via Toll Like Receptors, was involved, and this was supported by transfer experiments using antigen pulsed Myd88(-)/(-) B cells. These data suggest TLR dependent antigen processing by IL-4Ralpha-responsive B cells producing IL-13 contribute significantly to CD4(+) T cell-mediated protective immunity against N. brasiliensis infection

Comparação entre a adiposidade subcutânea dos hemicorpos direito e esquerdo Comparison between the subcutaneous adiposity of the right and left sides

O objetivo deste estudo foi comparar os níveis de adiposidade subcutânea dos hemicorpos direito e esquerdo e, posteriormente, analisar o impacto dessas informações para o estudo da composição corporal. Setenta e seis indivíduos fisicamente ativos, 47 homens (21,6 ± 4,3 anos) e 29 mulheres (21,0 ± 2,6 anos), fizeram parte da amostra. As espessuras das dobras cutâneas abdominal, suprailíaca, subescapular, tricipital, bicipital, axilar média e perna medial foram mensuradas com um compasso Lange. Em valores médios absolutos, as maiores diferenças verificadas foram de 0,9mm (6,9%) e 0,8mm (6,8%), na dobra cutânea suprailíaca de homens e mulheres, respectivamente. Entretanto, nenhuma diferença estatisticamente significante foi encontrada na comparação entre os lados, em ambos os sexos, nas sete dobras cutâneas analisadas (P > 0,05). Similarmente, quando os valores medidos foram aplicados em equações preditivas para a determinação da gordura corporal relativa, de acordo com o sexo, nenhuma diferença significante foi encontrada (P > 0,05). Os resultados sugerem que fatores como o erro técnico de medida do avaliador, o tipo de compasso e a escolha da equação preditiva a ser utilizada, provavelmente tenham maior impacto para a estimativa da composição corporal pelo método de espessura de dobras cutâneas do que o lado a ser adotado como referência para a obtenção das medidas.<br>The aim of this study was to compare subcutaneous adiposity levels of right and left sides and posteriorly to analyze the impact of this information to the body composition study. Seventy-six physically active individuals, 47 men (21.6 ± 4.3 years) and 29 women (21.0 ± 2.6 years), comprised the sample. Abdominal, suprailiac, subscapular, triceps, biceps, midaxillary and mid calf skinfolds were measured using the Lange caliper. In terms of mean absolute values, the largest differences found were 0.9 mm (6.9%) and 0.8 mm (6.8%) for the suprailiac skinfold in men and women, respectively. However, there was no significant difference in the comparison between the right and left sides of body for both genders in the seven examples of skinfold thickness analyzed (P > 0.05). Similarly, after applying the measured values of skinfold thickness in predictive equations, we found no significant differences in relative body fat in men and women (P > 0.05). The results suggest that factors such as the technical error of measurement of the examiner, the type of caliper and the choice of the predictive equation to be used probably have more impact on the estimation of body composition derived from skinfolds than the side of body measured