title: Reduced peripheral and mucosal Tropheryma whipplei-specific Th1 response in patients with Whipple's disease.
abstract: Whipple's disease is a rare infectious disorder caused by Tropheryma whipplei. Major symptoms are arthropathy, weight loss, and diarrhea, but the CNS and other organs may be affected, too. The incidence of Whipple's disease is very low despite the ubiquitous presence of T. whipplei in the environment. Therefore, it has been suggested that host factors indicated by immune deficiencies are responsible for the development of Whipple's disease. However, T. whipplei-specific T cell responses could not be studied until now, because cultivation of the bacteria was established only recently. Thus, the availability of T. whipplei Twist-Marseille(T) has enabled the first analysis of T. whipplei-specific reactivity of CD4(+) T cells. A robust T. whipplei-specific CD4(+) Th1 reactivity and activation (expression of CD154) was detected in peripheral and duodenal lymphocytes of all healthy (16 young, 27 age-matched, 11 triathletes) and disease controls (17 patients with tuberculosis) tested. However, 32 Whipple's disease patients showed reduced or absent T. whipplei-specific Th1 responses, whereas their capacity to react to other common Ags like tetanus toxoid, tuberculin, actinomycetes, Giardia lamblia, or CMV was not reduced compared with controls. Hence, we conclude that an insufficient T. whipplei-specific Th1 response may be responsible for an impaired immunological clearance of T. whipplei in Whipple's disease patients and may contribute to the fatal natural course of the disease.
authors.affiliation: Medizinische Klinik I, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany. verena.moss@charite.de
authors.forename: Verena
authors.initials: V
authors.lastname: Moos
authors.forename: Désirée
authors.initials: D
authors.lastname: Kunkel
authors.forename: Thomas
authors.initials: T
authors.lastname: Marth
authors.forename: Gerhard E
authors.initials: GE
authors.lastname: Feurle
authors.forename: Bernard
authors.initials: B
authors.lastname: LaScola
authors.forename: Ralf
authors.initials: R
authors.lastname: Ignatius
authors.forename: Martin
authors.initials: M
authors.lastname: Zeitz
authors.forename: Thomas
authors.initials: T
authors.lastname: Schneider
mesh_terms: D000192:Actinomycetales / Q000276:immunology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology / Q000821:virology; D002460:Cell Line; D002469:Cell Separation; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology*; D004386:Duodenum / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D004768:Enterotoxins / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013211:Staphylococcus aureus / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D008061:Whipple Disease / Q000276:immunology* / Q000382:microbiology / Q000821:virology
chemical_list: D000942:Antigens, Bacterial; D000956:Antigens, Viral; D004768:Enterotoxins; D018984:Epitopes, T-Lymphocyte; D007376:Interleukin-2; C031818:enterotoxin B, staphylococcal