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-beta 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-gamma 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, Treg 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. The Journal of Immunology, 2011, 187: 4061-4067.