Streptococcal superantigen-induced expansion of human tonsil T cells leads to altered T follicular helper cell phenotype, B cell death and reduced immunoglobulin release.

Streptococcal pyrogenic exotoxin (Spe) A expression is epidemiologically linked to streptococcal tonsillo-pharyngitis and outbreaks of scarlet fever, although the mechanisms by which superantigens confer advantage to Streptococcus pyogenes are unclear. S. pyogenes is an exclusively human pathogen. As the leucocyte profile of tonsil is unique, the impact of SpeA production on human tonsil cell function was investigated. Human tonsil cells from routine tonsillectomy were co-incubated with purified streptococcal superantigens or culture supernatants from isogenic streptococcal isolates, differing only in superantigen production. Tonsil cell proliferation was quantified by tritiated thymidine incorporation, and cell surface characteristics assessed by flow cytometry. Soluble mediators including immunoglobulin were measured using enzyme-linked immunosorbent assay. Tonsil T cells proliferated in response to SpeA and demonstrated typical release of proinflammatory cytokines. When cultured in the absence of superantigen, tonsil preparations released large quantities of immunoglobulin over 7 days. In contrast, marked B cell apoptosis and abrogation of total immunoglobulin (Ig)A, IgM, and IgG production occurred in the presence of SpeA and other superantigens. In SpeA-stimulated cultures, T follicular helper (Tfh) cells showed a reduction in C-X-C chemokine receptor (CXCR)5 (CD185) expression, but up-regulation of OX40 (CD134) and inducible T cell co-stimulator (ICOS) (CD278) expression. The phenotypical change in the Tfh population was associated with impaired chemotactic response to CXCL13. SpeA and other superantigens cause dysregulated tonsil immune function, driving T cells from Tfh to a proliferating phenotype, with resultant loss of B cells and immunoglobulin production, providing superantigen-producing bacteria with a probable survival advantage.

Molecular genotyping of HIV-1 in 61 patients with AIDS from Lomé, Togo.

To study the distribution of HIV types and genotypes, in Lomé, Togo, a random population of patients who met the clinical criteria of the Bangui definition of AIDS and were positive with two independent screening assays for antibodies to HIV-1 group M, HIV-2, and HIV-1 group O was selected. HIV RNA from serum samples was reverse-transcribed and amplified with degenerate primers annealing to conserved regions of the HIV-1, HIV-2, and HIV-O gag gene. Amplicons were directly sequenced using an automated sequencer. A 262-271-bp (strain-dependent) fragment of the gag gene from each patient was phylogenetically analyzed and compared to the corresponding gag sequences of published HIV-1 sequences of known African genotypes. Genotype A was found in 48 of 60 patient amplicons (80%), subdivided into two clusters. Ten patients (16.7%) were HIV-1 genotype G; one was genotype D and one genotype H. HIV-1 genotype B was not found. Amplicons from two patients contained sequence ambiguities, requiring cloning and sequencing of the gag insert. One patient (T52) was apparently infected with HIV-1 genotypes A and G; whereas HIV-1 from patient T139 was of genotype A, with 2/10 clones having a three-codon insertion at nucleotide position 1142 of the gag gene. HIV-1 genotype A is dominant in Togo; genotype G is frequent and genotype B has not been found.

Differences in early patterns of gonadotrophin secretion between early and late maturing bulls, and changes in semen characteristics at puberty.

In prepubertal bull calves there is an early transient rise in gonadotrophin secretion between 10 and 20 wk of age, and it has been suggested that this plays a role in the attainment of sexual maturation. To test this, we looked for differences in the gonadotrophin secretory pattern from birth to puberty between early and late maturing bulls. We also characterized the changes in semen morphology that occur about the time of puberty. Blood samples were collected (n=28) every wk from 2 to 20 wk of age and then every 2 wk until 50 wk of age. Semen was collected by electroejaculation at approximately 4-wk intervals from 36 to 49 wk of age. Puberty was defined as the first age at which an ejaculate contained 50 million spermatozoa with a minimum of 10 % motility Bulls were divided into early (n = 14) and late (n = 14) maturing groups based on the age at puberty (41.9 +/- 0.3 and 48.3 +/- 0.7 wk of age, respectively). There was a transient increase in serum concentrations of LH and FSH between 2 and 24 wk of age; LH concentrations were greater in early maturing bulls than in late maturing bulls at 12, 13, 15, 17 and 48 wk of age (P < 0.05). Serum concentrations of testosterone and FSH did not differ between groups (P > 0.05). As the bulls matured there was an increase in the percentage of normal and live sperm cells, cell motility and the number of cells per ejaculate (P < 0.05), and a decrease in the percentage of proximal droplets and knobbed acrosomes (P < 0.05). We concluded that, during the early rise in LH secretion, early maturing bulls had higher circulating LH concentrations than late maturing bulls. During the weeks preceding and following puberty there was an increase in the quality of semen collected by electroejaculation.