Modulation of systemic antigen-specific immune responses by oral antigen in humans |
| |
Authors: | Kapp Kerstin Maul Jochen Hostmann Arwed Mundt Pamela Preiss Jan C Wenzel Arlett Thiel Andreas Zeitz Martin Ullrich Reiner Duchmann Rainer |
| |
Institution: | Charité-Campus Benjamin Franklin, Medizinische Klinik I (Gastroenterologie, Infektiologie, Rheumatologie), Berlin, Germany. |
| |
Abstract: | Oral antigen uptake can induce systemic immune responses ranging from tolerance to immunity. However, the underlying mechanisms are poorly understood, especially in humans. Here, keyhole limpet hemocyanin (KLH), a neoantigen which has been used in earlier studies of oral tolerance, was fed in a repeated low-dose and a single high-dose protocol to healthy volunteers. KLH-specific CD4(+) T-cell proliferation and cytokine production, as well as KLH-specific serum Ab and the effects of oral KLH on a subsequent parenterally induced systemic immune response, were analyzed. Repeated low-dose oral KLH alone induced antigen-specific CD4(+) T cells positive predominantly for the gut-homing receptor integrin β7 and the cytokines IL-2 and TNF-α; some CD4(+) T cells also produced IL-4. Oral feeding of KLH accelerated a subsequent parenterally induced systemic CD4(+) T-cell response. The cytokine pattern of KLH-specific CD4(+) T cells shifted toward more IL-4- and IL-10- and less IFN-γ-, IL-2- and TNF-α-producing cells. The parenterally induced systemic KLH-specific B-cell response was accelerated and amplified by oral KLH. The impact of single high-dose oral KLH on antigen-specific immune responses was less pronounced compared with repeated low-dose oral KLH. These findings suggest that oral antigen can effectively modulate subsequently induced systemic antigen-specific immune responses. Immunomodulation by oral antigen may offer new therapeutic strategies for Th type1-mediated inflammatory diseases and for the development of vaccination strategies. |
| |
Keywords: | Cytokines Human Th1/Th2 cells Tolerance/Suppression/Anergy Vaccination |
本文献已被 PubMed 等数据库收录! |
|