Characterization of CD8+ T-cell response in acute and resolved hepatitis A virus infection.

BACKGROUND & AIMS: In contrast to the infection with other hepatotropic viruses, hepatitis A virus (HAV) always causes acute self-limited hepatitis, although the role for virus-specific CD8 T cells in viral containment is unclear. Herein, we analyzed the T cell response in patients with acute hepatitis by utilizing a set of overlapping peptides and predicted HLA-A2 binders from the polyprotein. METHODS: A set of 11 predicted peptides from the HAV polyprotein, identified as potential binders, were synthesized. Peripheral blood mononuclear cells (PBMCs) from patients were tested for IFNγ secretion after stimulation with these peptides and ex vivo with HLA-A2 tetramers. Phenotyping was carried out by staining with the activation marker CD38 and the memory marker CD127. RESULTS: Eight out of 11 predicted HLA-A2 binders showed a high binding affinity and five of them were recognized by CD8+ T cells from patients with hepatitis A. There were significant differences in the magnitude of the responses to these five peptides. One was reproducibly immunodominant and the only one detectable ex vivo by tetramer staining of CD8+ T cells. These cells have an activated phenotype (CD38hi CD127lo) during acute infection. Three additional epitopes were identified in HLA-A2 negative patients, most likely representing epitopes restricted by other HLA-class I-alleles (HLA-A11, B35, B40). CONCLUSIONS: Patients with acute hepatitis A have a strong multi-specific T cell response detected by ICS. With the tetramer carrying the dominant HLA-A2 epitope, HAV-specific and activated CD8+ T cells could be detected ex vivo. This first description of the HAV specific CTL-epitopes will allow future studies on strength, breadth, and kinetics of the T-cell response in hepatitis A.

[Functional abdominal pain in childhood]. / Funktioneller Bauchschmerz im Kindesalter.

Functional abdominal pain is one of the most common types of recurrent pediatric pain. This paper gives an overview of the etiopathogenesis, diagnostic criteria, and cognitive-behavioral intervention strategies for functional abdominal pain. It addresses the issues of organic causes, psychosocial stressors, and family and social conditions, as well as operant processes.

Therapeutic vaccination in chronic hepatitis B: preclinical studies in the woodchuck model.

Interferon-alpha and nucleoside analogues are available for the treatment of chronic hepatitis B virus (HBV) infection but do not lead to a satisfactory result. New findings about the immunological control of HBV during acute infection suggest the pivotal role of T-cell mediated immune responses. Several preclinical and clinical trials were undertaken to explore the possibility of stimulating specific immune responses in chronically infected animals and patients by vaccination. However, vaccination with commercially available HBV vaccines in patients and immunization in woodchucks with core or surface proteins of woodchuck hepatitis virus (WHV) did not result in effective control of HBV and WHV infection, suggesting that new formulations of therapeutic vaccines are needed. Some new approaches combining antiviral treatments with nucleoside analogues, DNA vaccines and protein vaccines were tested in the woodchuck model. It could be shown that therapeutic vaccinations are able to stimulate specific B- and T-cell responses and to achieve transient suppression of viral replication. These results suggest the great potential of therapeutic vaccination in combination with antivirals to reach an effective and sustained control of HBV infection.

[Nursing and suckling behavior and mother-child contacts in domestic rabbits]. / Untersuchungen zum Säuge- und Saugverhalten und zur Mutter-Kind-Beziehung bei Hauskaninchen.

Investigations with 34 litters of rabbits breed White New Zealands by the help of infrared videotechnique over 242 day-night-periods (24 hr per period) showed a frequency of 15.1 mother-child-contacts on average of 24 hr (Min: 6, Max: 48 contacts a day). In 38% of all 24-hr-cycles observed one suckling event was found and in 56.6% of all cases two up to five suckling periods were seen (5.4% of all 24-hr-periods were without suckling). Mean suckling frequency per 24 hr was 1.83 with maximum in second suckling week (2.31). Highly significant positive coefficients of correlation (r = 0.33 up to r = 0.89) were found between birth weight, daily gain, milk intake and weaning weight. Mother-child-relations in rabbits (breed White New Zealands) are more intensive as thought up to now so that the separation of mother from her litter represents an intervention into species-specific behaviour.