Although it is well established that microbial infections predispose to autoimmune diseases, the underlying mechanisms remain poorly understood. After infection, tissue-resident memory T (TRM) cells persist in peripheral organs and provide immune protection against reinfection. However, whether TRM cells participate in responses unrelated to the primary infection, such as autoimmune inflammation, is unknown. By using high-dimensional single-cell analysis, we identified CD4+ TRM cells with a TH17 signature (termed TRM17 cells) in kidneys of patients with ANCA-associated glomerulonephritis. Experimental models demonstrated that renal TRM17 cells were induced by pathogens infecting the kidney, such as Staphylococcus aureus, Candida albicans, and uropathogenic Escherichia coli, and persisted after the clearance of infections. Upon induction of experimental glomerulonephritis, these kidney TRM17 cells rapidly responded to local proinflammatory cytokines by producing IL-17A and thereby exacerbate renal pathology. Thus, our data show that pathogen-induced TRM17 cells have a previously unrecognized function in aggravating autoimmune disease.

The combined hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio Haemophilus influenzae type b (DTPa-HBV-IPV/Hib) vaccine produces similar hepatitis B responses as the HBV monovalent vaccine. Booster vaccination of immunocompetent individuals primed against hepatitis B in infancy is currently not recommended. We investigated persisting immunity to hepatitis B in 4-6 (Study A; 106745) and 7-9 (Study B; 106744) year-old children primed in infancy and boosted in the second year of life with DTPa-HBV-IPV/Hib. Immunity was assessed by measuring persisting anti-HBs antibodies and evaluating the response to a challenge dose of HBV vaccine. At 4-6 years of age 86.0% of 186 subjects had persisting anti-HBs > or =10 mIU/ml increasing to 98.4% after the challenge. At 7-9 years of age, 78.0% of 186 subjects continued to have anti-HBs antibody concentrations > or =10 mIU/ml, increasing to 98.9% after the challenge. In both studies anti-HBs antibody GMC rose >80-fold. An anamnestic response to the HBV challenge was observed in 95.7% and 98.9% of subjects in Studies A and B, respectively. In both studies, 87% of 38 subjects with initially undetectable circulating anti-HBs antibodies (>3.3 IU/ml) achieved the 10 mIU/ml threshold after challenge; > or =97.0% of subjects with detectable antibodies before the challenge at least quadrupled their concentration. Post-vaccination anti-HBs concentrations were directly related to persisting antibody concentrations and the concentrations achieved after the booster dose in the second year of life. The HBV vaccine challenge dose was well tolerated. These studies show that primary and booster vaccination with combined DTPa-HBV-IPV/Hib (Infanrix hexa) induces sustained immune memory against hepatitis B up to age 9 years.

Subacute sclerosing panencephalitis (SSPE) is a demyelinating central nervous system disease caused by a persistent measles virus (MV) infection of neurons and glial cells.There is still no specific therapy available, and in spite of an intact innate and adaptive immune response, SSPE leads inevitably to death. In order to select effective antiviral short interfering RNAs (siRNAs), we established a plasmid-based test system expressing the mRNA of DsRed2 fused with mRNA sequences of single viral genes, to which certain siRNAs were directed. siRNA sequences were expressed as short hairpin RNA (

Combination vaccines induce immunity against multiple diseases in a single injection and thus facilitate delivery of complex vaccination schedules. Use of combination vaccines increases both vaccine coverage and the timeliness of vaccination.1 Infanrix hexa TM , the combined hexavalent diphtheria-tetanus-pertussis-hepatitis B-inactivated poliomyelitis-Haemophilus influenzae type b conjugate vaccine [DTPa-HBV-IPV/Hib, GlaxoSmithKline Biologicals (GSK), Rixensart, Belgium] is the only hexavalent vaccine currently licensed for primary and booster vaccination of infants and provides simultaneous protection against six major diseases of childhood. DTPa-HBV-IPV/Hib contains ≥30 IU diphtheria toxoid, ≥40 IU tetanus toxoid, 25 μg pertussis toxin (PT), 25 μg filamentous haemagglutinin (FHA), 8 μg pertactin (PRN), 10 μg recombinant HBsAg, 40D, 8D and 32D antigen units of poliovirus types 1, 2 and 3 respectively and 10 μg Hib polyribosylribitol-phosphate (PRP) conjugated to tetanus toxoid.Background: the combined diphtheria-tetanus-pertussis-hepatitis B-inactivated poliomyelitis-Haemophilus influenzae conjugate vaccine (Dtpa-HBV-IpV/Hib, Infanrix Hexa tM GlaxoSmithKline Biologicals, rixensart, Belgium) is the only hexavalent vaccine currently licensed for primary and booster vaccination of infants and provides simultaneous protection against six major diseases of childhood. the persistence of the immune response in children aged 4-6 and 7-9 years of age previously vaccinated with four doses of Dtpa-HBV-IpV/Hib vaccine was assessed (www.clinical trials.gov.au 106744 NCt00356564 and 106745 NCt00335881).Methods: A blood sample was collected from 403 children, all of whom had received 3-dose primary vaccination and a booster dose in the second year of life with Dtpa-HBV-IpV/Hib, in previous clinical vaccine trials in Germany.results: Mean time from the fourth Dtpa-HBV-IpV/Hib dose until serological follow-up ranged between 3.6 and 6.4 years. After the 4 th Dtpa-HBV-IpV/Hib dose, in subjects who had not received additional booster doses, seroprotective antibody levels persisted up to 9 years of age in ≥90% of subjects for diphtheria, Hib and poliomyelitis, in 77.2% subjects for Hepatitis B and in 64.7% of subjects for tetanus. Anti-pertussis toxin antibodies remained detectable in no more than 38.2% of subjects.Conclusion: With the exception of pt, the combined Dtpa-HBV-IpV/Hib induces long lasting immune response against all vaccine antigens. Falling seropositivity against pt over time supports the recommended administration of a pertussis booster dose in 5-6 year old children in Germany.