Human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T(EMRA) cells in early infection are linked to control of HIV-1 viremia and predict the subsequent viral load set point

CD8(+) T cells are believed to play an important role in the control of human immunodeficiency virus type 1 (HIV-1) infection. However, despite intensive efforts, it has not been possible to consistently link the overall magnitude of the CD8(+) T-cell response with control of HIV-1. Here, we have investigated the association of different CD8(+) memory T-cell subsets responding to HIV-1 in early infection with future control of HIV-1 viremia. Our results demonstrate that both a larger proportion and an absolute number of HIV-1-specific CD8(+) CCR7(-) CD45RA(+) effector memory T cells (T(EMRA) cells) were associated with a lower future viral load set point. In contrast, a larger absolute number of HIV-1-specific CD8(+) CCR7(-) CD45RA(-) effector memory T cells (T(EM)) was not related to the viral load set point. Overall, the findings suggest that CD8(+) T(EMRA) cells have superior antiviral activity and indicate that both qualitative and quantitative aspects of the CD8(+) T-cell response need to be considered when defining the characteristics of protective immunity to HIV-1.     

Insertion of leader peptidase into the thylakoid membrane during synthesis in a chloroplast translation system

The mechanisms of targeting and insertion of chloroplast-encoded thylakoid membrane proteins are poorly understood. In this study, we have used a translation system isolated from chloroplasts to begin to investigate these mechanisms. The bacterial membrane protein leader peptidase (Lep) was used as a model protein because its targeting and insertion mechanisms are well understood for Escherichia coli and for the endoplasmic reticulum. Lep could thus provide insight into the functional homologies between the different membrane systems. Lep was efficiently expressed in the chloroplast translation system, and the protein could be inserted into thylakoid membranes with the same topology as in E. coli cytoplasmic membranes, following the positive-inside rule. Insertion of Lep into the thylakoid membrane was stimulated by the trans-thylakoid proton gradient and was strongly inhibited by azide, suggesting a requirement for SecA activity. Insertion most likely occurred in a cotranslational manner, because insertion could only be observed if thylakoid membranes were present during translation reactions but not when thylakoid membranes were added after translation reactions were terminated. To halt the elongation process at different stages, we translated truncated Lep mRNAs without a stop codon, resulting in the formation of stable ribosome nascent chain complexes. These complexes showed a strong, salt-resistant affinity for the thylakoid membrane, implying a functional interaction of the ribosome with the membrane and supporting a cotranslational insertion mechanism for Lep. Our study supports a functional homology for the insertion of Lep into the thylakoid membrane and the E. coli cytoplasmic membrane.     

Helicobacter pylori infection in childhood: risk factors and effect on growth.

OBJECTIVE--To investigate the current prevalence of Helicobacter pylori infection in childhood, the risk factors for infection, and the effect of infection on growth in preadolescent schoolchildren. DESIGN--Population based sample of 7 year old schoolchildren followed up at age 11; data on risk factors for infection collected at age 7; presence of infection at age 11 determined by measurement of salivary IgG against H pylori by a newly developed enzyme linked immunosorbent assay (ELISA). Height was measured at 7 and 11 years of age. SUBJECTS--554 schoolchildren from Edinburgh. RESULTS--62 (11%) children had H pylori infection. Independent risk factors for infection were single parent families (adjusted odds ratio = 2.5; 95% confidence interval 1.1 to 5.7), the 10% most crowded homes (3.1; 1.3 to 7.2), and schools serving predominantly rented housing estates (2.5; 1.0 to 6.5). School catchment area was more important than parental social class or housing tenure. Growth in height between 7 and 11 was diminished in infected children by a mean of 1.1 cm (0.3 to 2.0 cm) over four years. This growth reduction was largely confined to girls (1.6 cm over four years), among whom it correlated with salivary IgG (P = 0.015). CONCLUSION--Data from salivary assay to investigate the epidemiology of H pylori suggest that factors relating to the type of community in which the child lives may now be as important for acquisition of this infection as features of the family home. The greater reduction of growth among infected girls raises the possibility that H pylori infection may delay or diminish the pubertal growth spurt.     

Large scale analysis of pediatric antiviral CD8+ T cell populations reveals sustained, functional and mature responses

Background

Cellular immunity plays a crucial role in cytomegalovirus (CMV) infection and substantial populations of CMV-specific T cells accumulate throughout life. However, although CMV infection occurs during childhood, relatively little is know about the typical quantity and quality of T cell responses in pediatric populations.

Methods

One thousand and thirty-six people (Male/Female = 594/442, Age: 0–19 yr.; 959 subjects, 20–29 yr.; 77 subjects) were examined for HLA typing. All of 1036 subjects were tested for HLA-A2 antigen. Of 1036 subjects, 887 were also tested for HLA-A23, 24 antigens. In addition, 50 elderly people (Male/Female = 11/39, Age: 60–92 yr.) were also tested for HLA-A2 antigen. We analyzed the CD8+ T cell responses to CMV, comparing these to responses in children and young. The frequencies, phenotype and function CD8+ T cells for two imunodominant epitopes from pp65 were measured.

Results

We observed consistently high frequency and phenotypically "mature" (CD27 low, CD28 low, CD45RA+) CMV-specific CD8+ T cell responses in children, including those studied in the first year of life. These CD8+ T cells retained functionality across all age groups, and showed evidence of memory "inflation" only in later adult life.

Conclusion

CMV consistently elicits a very strong CD8+ T cell response in infants and large pools of CMV specific CD8+ T cells are maintained throughout childhood. The presence of CMV may considerably mould the CD8+ T cell compartment over time, but the relative frequencies of CMV-specific cells do not show the evidence of a population-level increase during childhood and adulthood. This contrast with the marked expansion ("inflation") of such CD8+ T cells in older adults. This study indicates that large scale analysis of peptide specific T cell responses in infants is readily possible. The robust nature of the responses observed suggests vaccine strategies aimed at priming and boosting CD8+ T cells against major pathogens (including HIV, malaria and CMV itself) could be successful in this age-group.     

From descriptive to predictive distribution models: a working example with Iberian amphibians and reptiles

Background

The two sympatric species of Tunisian desert ants, Cataglyphis bicolor and C. mauritanica, do not exhibit any differences in their foraging ecology, e.g. in food preferences and in their spatial and temporal activity patterns. Here we show that instead the two species markedly differ in their life histories.

Results

We analysed mtDNA of specimens that were collected along a 250-km transect. C. bicolor exhibited a genetically unstructured population (with the genetic and geographic distances among colonies not being correlated). On the contrary the populations of the polygynous C. mauritanica were clearly structured, i.e. exhibited a strong correlation between genetic and geographic distances. This difference is in accordance with large queen dispersal distances due to far-reaching mating flights in C. bicolor and small queen dispersal distances due to colony foundation by budding in C. mauritanica. Furthermore, wherever we found populations of both species to coexist within the same habitat, the habitat was used agriculturally. Mapping nest positions over periods of several years showed that plowing dramatically decreased the nest densities of either species.

Conclusion

We conclude that owing to its greater queen dispersal potential C. bicolor might be more successful in quickly re-colonizing disturbed areas, while the slowly dispersing C. mauritanica could later out-compete C. bicolor by adopting its effective nest-budding strategy. According to this scenario the observed sympatry of the two species might be an intermediate stage in which faster colonization by one species and more powerful exploitation of space by the other species have somehow balanced each other out. In conclusion, C. bicolor and C. mauritanica represent an example where environmental disturbances in combination with different life histories might beget sympatry in congeneric species with overlapping niches.     

Interaction between Cu toxicity and P deficiency in soil-grown cowpea (Vigna unguiculata (L.) Walp.)

Anthropogenic contamination with Cu is an important issue and it is necessary to understand how Cu toxicity influences the uptake/acquisition of nutrients by plants. An experiment was conducted with soil-grown cowpea (Vigna unguiculata (L.) Walp.) to investigate the interaction between Cu toxicity and P deficiency. Plant performance was related to the activity of Cu²⁺ at the outer surface of the root plasma membrane, {Cu²⁺} ₀ ^o , which was calculated from properties of the soil solution. The addition of Cu to the soil was found to reduce growth of plant shoots by inducing Cu toxicity, which was associated with a reduction in the shoot tissue Fe concentration. The critical value (50% reduction in shoot growth) determined for {Cu²⁺} ₀ ^o in this soil-based experiment (3.8 μM) corresponds well to values determined previously. Importantly, regression analyses indicated that although the alleviation of P deficiency improved overall growth, the P-status of the plant did not influence the apparent toxicity of the Cu. This result was unexpected, given that Cu inhibits the growth of roots hairs; these being important for the uptake of immobile nutrients such as P. This study advances our understanding of Cu toxicity and its impact upon nutrient uptake.