title: Regulatory T cells in patients with Whipple's disease.
abstract: Classical Whipple's disease (CWD) is caused by chronic infection with Tropheryma whipplei that seems to be associated with an underlying immune defect. The pathognomonic hallmark of CWD is a massive infiltration of the duodenal mucosa with T. whipplei-infected macrophages that disperse systemically to many other organ systems. An alleviated inflammatory reaction and the absence of T. whipplei-specific Th1 reactivity support persistence and systemic spread of the pathogen. In this article, we hypothesized that regulatory T cells (T(reg)) are involved in immunomodulation in CWD, and we asked for the distribution, activation, and regulatory capacity of T(reg) in CWD patients. Whereas in the lamina propria of CWD patients before treatment numbers of T(reg) were increased, percentages in the peripheral blood were similar in CWD patients and healthy controls. However, peripheral T(reg) of CWD patients were more activated than those of controls. Elevated secretion of IL-10 and TGF-β in the duodenal mucosa of CWD patients indicated locally enhanced T(reg) activity. Enhanced CD95 expression on peripheral memory CD4(+) T cells combined with reduced expression of IFN-γ and IL-17A upon polyclonal stimulation by CD4(+) cells from untreated CWD patients further hinted to T(reg) activity-related exhaustion of effector CD4(+) T cells. In conclusion, increased numbers of T(reg) can be detected within the duodenal mucosa in untreated CWD, where huge numbers of T. whipplei-infected macrophages are present. Thus, T(reg) might contribute to the chronic infection and systemic spread of T. whipplei in CWD but in contrast prevent mucosal barrier defect by reducing local inflammation.
authors.affiliation: Medizinische Klinik I, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, D-12203 Berlin, Germany.
authors.forename: Katina
authors.initials: K
authors.lastname: Schinnerling
authors.forename: Verena
authors.initials: V
authors.lastname: Moos
authors.forename: Anika
authors.initials: A
authors.lastname: Geelhaar
authors.forename: Kristina
authors.initials: K
authors.lastname: Allers
authors.forename: Christoph
authors.initials: C
authors.lastname: Loddenkemper
authors.forename: Julian
authors.initials: J
authors.lastname: Friebel
authors.forename: Kristina
authors.initials: K
authors.lastname: Conrad
authors.forename: Anja A
authors.initials: AA
authors.lastname: Kühl
authors.forename: Ulrike
authors.initials: U
authors.lastname: Erben
authors.forename: Thomas
authors.initials: T
authors.lastname: Schneider
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002469:Cell Separation; D016207:Cytokines / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D054851:Tropheryma / Q000276:immunology; D008061:Whipple Disease / Q000276:immunology* / Q000382:microbiology
chemical_list: D016207:Cytokines