The ST3Gal-I Sialyltransferase Controls CD8+ T Lymphocyte Homeostasis by Modulating O-Glycan Biosynthesis

The effects of sex hormones on immune function have received much attention, especially following the proposal of the immunocompetence handicap hypothesis. Many studies, both experimental and correlational, have been conducted to test the relationship between immune function and the sex hormones testosterone in males and oestrogen in females. However, the results are mixed. We conducted four cross-species meta-analyses to investigate the relationship between sex hormones and immune function: (i) the effect of testosterone manipulation on immune function in males, (ii) the correlation between circulating testosterone level and immune function in males, (iii) the effect of oestrogen manipulation on immune function in females, and (iv) the correlation between circulating oestrogen level and immune function in females. The results from the experimental studies showed that testosterone had a medium-sized immunosuppressive effect on immune function. The effect of oestrogen, on the other hand, depended on the immune measure used. Oestrogen suppressed cell-mediated immune function while reducing parasite loads. The overall correlation (meta-analytic relationship) between circulating sex hormone level and immune function was not statistically significant for either testosterone or oestrogen despite the power of meta-analysis. These results suggest that correlational studies have limited value for testing the effects of sex hormones on immune function. We found little evidence of publication bias in the four data sets using indirect tests. There was a weak and positive relationship between year of publication and effect size for experimental studies of testosterone that became non-significant after we controlled for castration and immune measure, suggesting that the temporal trend was due to changes in these moderators over time. Graphical analyses suggest that the temporal trend was due to an increased use of cytokine measures across time. We found substantial heterogeneity in effect sizes, except in correlational studies of testosterone, even after we accounted for the relevant random and fixed factors. In conclusion, our results provide good evidence that testosterone suppresses immune function and that the effect of oestrogen varies depending on the immune measure used.

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The effects of sex hormones on immune function: a meta-analysis.

Recent studies have demonstrated the need for complementing cellular genomic information with specific information on expressed proteins, or proteomics, since the correlation between the two is poor. Typically, proteomic information is gathered by analyzing samples on two-dimensional gels with the subsequent identification of specific proteins of interest by using trypsin digestion and mass spectrometry in a process termed peptide mass fingerprinting. These procedures have, as a rule, been labor-intensive and manual, and therefore of low throughput. The development of automated proteomic technology for processing large numbers of samples simultaneously has made the concept of profiling entire proteomes feasible at last. In this study, we report the initiation of the (eventual) complete profile of the rat mitochondrial proteome by using high-throughput automated equipment in combination with a novel fractionation technique using minispin affinity columns. Using these technologies, approximately one hundred proteins could be identified in several days. In addition, separate profiles of calcium binding proteins, glycoproteins, and hydrophobic or membrane proteins could be generated. Because mitochondrial dysfunction has been implicated in numerous diseases, such as cancer, Alzheimer's disease and diabetes, it is probable that the identification of the majority of mitochondrial proteins will be a beneficial tool for developing drug and diagnostic targets for associated diseases.

High-throughput profiling of the mitochondrial proteome using affinity fractionation and automation.

Schistosomiasis is a major neglected tropical disease that afflicts more than 240 million people, including many children and young adults, in the tropics and subtropics. The disease is characterized by chronic infections with significant residual morbidity and is of considerable public health importance, with substantial socioeconomic impacts on impoverished communities. Morbidity reduction and eventual elimination through integrated intervention measures are the focuses of current schistosomiasis control programs. Precise diagnosis of schistosome infections, in both mammalian and snail intermediate hosts, will play a pivotal role in achieving these goals. Nevertheless, despite extensive efforts over several decades, the search for sensitive and specific diagnostics for schistosomiasis is ongoing. Here we review the area, paying attention to earlier approaches but emphasizing recent developments in the search for new diagnostics for schistosomiasis with practical applications in the research laboratory, the clinic, and the field. Careful and rigorous validation of these assays and their cost-effectiveness will be needed, however, prior to their adoption in support of policy decisions for national public health programs aimed at the control and elimination of schistosomiasis.

Advances in the Diagnosis of Human Schistosomiasis

Applications of affinity chromatography in proteomics.

A nested polymerase chain reaction (PCR) protocol was developed for detecting the presence of Schistosoma mansoni sporocysts in intermediate host snails of the genus Biomphalaria. To accomplish this, rDNA genes encoding the 18S rRNA of S. mansoni and Biomphalaria alexandrina from Egypt were sequenced, as were 18S-encoding genes of the 13-16-R1 and Salvador strains of Biomphalaria glabrata. Based on a comparison of host and parasite sequences, a nested set of PCR primers was designed to allow specific amplification of portions of S. mansoni 18S rDNA. These primers allowed detection of as little as 10 fg of S. mansoni DNA diluted in 100 ng of snail DNA and did not allow amplification of snail 18S sequences. Using nested PCR, the presence of a single S. mansoni sporocyst within an adult snail could be detected at 1 day postexposure. In DNA samples extracted from each of 74 snails of the M-line strain of B. glabrata exposed to from 1 to 10 S. mansoni miracidia for intervals ranging from 1 to 44 days, use of the outside primer pair alone detected the parasite's presence in 51% of the snails, whereas the sequential use of outside and nested primer pairs detected parasites in 92% of the snails. This approach has utility in determining if snails in endemic areas bear prepatent or inactive infections and in assessing the degree of compatibility between local snail and schistosome populations. It will also facilitate studies of resistance of snails to infection.

Detection of Schistosoma mansoni in Biomphalaria using nested PCR.

Seasonal distribution and hormonal modulation of reptilian T cells

Characterization of Biomphalaria alexandrina-derived lectins recognizing a fucosyllactose-related determinant on schistosomes.

ABSTRAcr: Utilizing a Biomphalaria alexandrina-derived lectin (BaSII) of proven specificity to a Schistosoma mansoni-associated fucosyllactose [(Fuc al-2)Gal 31-4 Glc] determinant, a 37-kDa determinant-bearing glycoprotein (Sm 37) was identified selectively on adult male schistosomes. Sm 37 was purified to homogeneity from extracts of adult male worms metabolically radiolabeled with [35S] methionine by BaSII affinity chromatography followed by separation on an HPLC column. Treatments with endoglycosidases, alkaline borohydride, as well as serial lectin affinity chromatography and analysis on 2-dimensional gels indicated that Sm 37 is synthesized as a 33-kDa polypeptide backbone that expresses the fucosyllactose determinant on the outer chain of a single N-linked complex-type glycan unit of either the biantennary or, to a lesser extent, the tri- or tetra-antennary types. The distinct structures of the complex oligosaccharides accounted for the expression of 2 isomorphs of Sm 37. The glycoprotein lacks other conventional high mannose-type or O-linked oligosaccharides and, as deduced from the N-terminal amino acid sequence, the Sm 37 polypeptide may be distinct from other schistosome polypeptides of known sequence. Based on the structural relatedness of the Sm 37-associated fucosyllactose determinant to the antigenic blood group H trisaccharide, these observations may have implications for mechanisms of these host-parasite interactions.

https://www.jstor.org/stable/info/3283782

Purification and characterization of SM 37: a fucosyllactose determinant-bearing glycoprotein probed by a Biomphalaria alexandrina lectin on adult male schistosomes.

Living lymphocytes of the adult lizard Agama stellio were examined for surface immunoglobulin (Ig) utilizing an antiserum specific for Agama γ-globulin (RAGS) raised in rabbits. In indirect immunofluorescence, 44% of bone marrow lymphocytes, 29% of splenic lymphocytes, 25% of peripheral blood lymphocytes and 7% of thymocytes exhibited readily demonstrable surface Ig determinants. Observations on shedding and resynthesis justified the endogenous production of these Ig molecules by Agama lymphocytes and ruled out false scoring due to cytophilic antibodies. Following interaction with AAGS in a temperature-controlled reaction, redistribution of the Ig-AAGS complexes into separable stages of patches, 1/2 caps, 1/4 caps, tight caps, shedding and re-expression was in a manner comparable to that cited for mammalian Ig molecules. Studies on the rate of capping and resynthesis demonstrated, however, that the processes were extremely prolonged compared to those observed in mammals and that the lymphocytes were not induced to transitional movement throughout. In terms of the ease of detectability, cross-reactivity with serum Ig, accessibility to AAGS and capping and resynthesis rates, no considerable differences in the Ig molecules of thymic and peripheral lymphocytes were observed. The Ig-bearing lymphocytes seemed to constitute a homogeneous population, which expresses selectivity in its representation within the various lymphoid compartments. The minority of Ig-bearing thymic lymphocytes was suggested to have a preferential homing capacity to the thymus environment in response to the total absence of GALT in this animal model. In structural terms, the present study suggests the possible delineation of lymphocytes into Ig-positive B-like and Ig-negative T-like lymphocytes at this evolutionary level.

Mohamed H. Mansour

Papers

Detection of Schistosoma mansoni in Biomphalaria using nested PCR.

Seasonal distribution and hormonal modulation of reptilian T cells

Characterization of Biomphalaria alexandrina-derived lectins recognizing a fucosyllactose-related determinant on schistosomes.

Purification and characterization of SM 37: a fucosyllactose determinant-bearing glycoprotein probed by a Biomphalaria alexandrina lectin on adult male schistosomes.

Phylogenesis of lymphocyte diversity. I. Immunoglobulin determinants on the lymphocyte surface of the lizard Agama stellio.