Loss of Immunization-Induced Epitope-Specific CD4 T-Cell Response following Anaplasma marginale Infection Requires Presence of the T-Cell Epitope on the Pathogen and Is Not Associated with an Increase in Lymphocytes Expressing Known Regulatory Cell Phenotypes
| Autor: | Glen A. Scoles, Eric L. Sutten, Joshua E. Turse, Wendy C. Brown, Wendell C. Johnson, Paulraj K. Lawrence, James R. Deringer, Junzo Norimine, Sushan Han |
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| Rok vydání: | 2015 |
| Předmět: |
Microbiology (medical)
Anaplasmosis Immunogen T cell Clinical Biochemistry Immunology Epitopes T-Lymphocyte Spleen Biology Peripheral blood mononuclear cell Epitope Immunophenotyping Microbiology T-Lymphocyte Subsets Immune Tolerance medicine Animals Immunology and Allergy IL-2 receptor Pathogen Cell Proliferation FOXP3 Virology Anaplasma marginale Phenotype medicine.anatomical_structure Cattle Immunization Clinical Immunology |
| Zdroj: | Clinical and Vaccine Immunology. 22:742-753 |
| ISSN: | 1556-679X 1556-6811 |
| Popis: | We have shown that in cattle previously immunized with outer membrane proteins, infection withAnaplasma marginaleinduces a functionally exhausted CD4 T-cell response to theA. marginaleimmunogen. Furthermore, T-cell responses following infection in nonimmunized cattle had a delayed onset and were sporadic and transient during persistent infection. The induction of an exhausted T-cell response following infection presumably facilitates pathogen persistence. In the current study, we hypothesized that the loss of epitope-specific T-cell responses requires the presence of the immunizing epitope on the pathogen, and T-cell dysfunction correlates with the appearance of regulatory T cells. In limited studies in cattle, regulatory T cells have been shown to belong to γδ T-cell subsets rather than be CD4 T cells expressing forkhead box protein P3 (FoxP3). Cattle expressing the DRB3*1101 haplotype were immunized with a truncatedA. marginalemajor surface protein (MSP) 1a that contains a DRB3*1101-restricted CD4 T-cell epitope, F2-5B. Cattle either remained unchallenged or were challenged withA. marginalebacteria that express the epitope or withA. marginalesubsp.centralethat do not. Peripheral blood and spleen mononuclear cells were monitored for MSP1a epitope F2-5B-specfic T-cell proliferative responses and were stained for γδ T-cell subsets or CD4+CD25+FoxP3+T cells before and during infection. As hypothesized, the induction of T-cell exhaustion occurred only following infection withA. marginale, which did not correlate with an increase in either CD4+CD25+FoxP3+T cells or any γδ T-cell subset examined. |
| Databáze: | OpenAIRE |
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