Peripheral T-Cell Reactivity to Heat Shock Protein 70 and Its Cofactor GrpE from Tropheryma whipplei Is Reduced in Patients with Classical Whipple's Disease
| Autor: | Kristina Allers, Verena Moos, Lucia Trotta, Gino Roberto Corazza, Kathleen Weigt, Thomas Schneider, Anika Geelhaar-Karsch, Ulrike Erben, Katina Schinnerling, Federico Biagi, Gerrit Oelkers |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male 0301 basic medicine Duodenum 030106 microbiology Immunology Tropheryma CD8-Positive T-Lymphocytes Lymphocyte Activation Microbiology Tropheryma whipplei Interferon-gamma Young Adult 03 medical and health sciences Bacterial Proteins Antigen Antigens CD Humans HSP70 Heat-Shock Proteins Intestinal Mucosa Heat-Shock Proteins Aged Aged 80 and over Host Response and Inflammation B-Lymphocytes CD40 biology Degranulation Middle Aged Flow Cytometry biology.organism_classification Hsp70 Granzyme B 030104 developmental biology Infectious Diseases Perforin Leukocytes Mononuclear biology.protein Female Parasitology Whipple Disease CD8 |
| Zdroj: | Infection and Immunity. 85 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.00363-17 |
| Popis: | Classical Whipple's disease (CWD) is characterized by the lack of specific Th1 response toward Tropheryma whipplei in genetically predisposed individuals. The cofactor GrpE of heat shock protein 70 (Hsp70) from T. whipplei was previously identified as a B-cell antigen. We tested the capacity of Hsp70 and GrpE to elicit specific proinflammatory T-cell responses. Peripheral mononuclear cells from CWD patients and healthy donors were stimulated with T. whipplei lysate or recombinant GrpE or Hsp70 before levels of CD40L, CD69, perforin, granzyme B, CD107a, and gamma interferon (IFN-γ) were determined in T cells by flow cytometry. Upon stimulation with total bacterial lysate or recombinant GrpE or Hsp70 of T. whipplei , the proportions of activated effector CD4 + T cells, determined as CD40L + IFN-γ + , were significantly lower in patients with CWD than in healthy controls; CD8 + T cells of untreated CWD patients revealed an enhanced activation toward unspecific stimulation and T. whipplei -specific degranulation, although CD69 + IFN-γ + CD8 + T cells were reduced upon stimulation with T. whipplei lysate and recombinant T. whipplei -derived proteins. Hsp70 and its cofactor GrpE are immunogenic in healthy individuals, eliciting effective responses against T. whipplei to control bacterial spreading. The lack of specific T-cell responses against these T. whipplei -derived proteins may contribute to the pathogenesis of CWD. |
| Databáze: | OpenAIRE |
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