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Characterization of the HCMV-Specific CD4 T Cell Responses that Are Associated with Protective Immunity

Please always quote using this URN: urn:nbn:de:bvb:20-opus-151462
  • Most humans become infected with human cytomegalovirus (HCMV). Typically, the immune system controls the infection, but the virus persists and can reactivate in states of immunodeficiency. While substantial information is available on the contribution of CD8 T cells and antibodies to anti-HCMV immunity, studies of the T\(_{H}\)1, T\(_{H}\)2, and T\(_{H}\)17 subsets have been limited by the low frequency of HCMV-specific CD4 T cells in peripheral blood mononuclear cell (PBMC). Using the enzyme-linked Immunospot\(^{®}\) assay (ELISPOT) thatMost humans become infected with human cytomegalovirus (HCMV). Typically, the immune system controls the infection, but the virus persists and can reactivate in states of immunodeficiency. While substantial information is available on the contribution of CD8 T cells and antibodies to anti-HCMV immunity, studies of the T\(_{H}\)1, T\(_{H}\)2, and T\(_{H}\)17 subsets have been limited by the low frequency of HCMV-specific CD4 T cells in peripheral blood mononuclear cell (PBMC). Using the enzyme-linked Immunospot\(^{®}\) assay (ELISPOT) that excels in low frequency measurements, we have established these in a sizable cohort of healthy HCMV controllers. Cytokine recall responses were seen in all seropositive donors. Specifically, interferon (IFN)-\({\gamma}\) and/or interleukin (IL)-17 were seen in isolation or with IL-4 in all test subjects. IL-4 recall did not occur in isolation. While the ratios of T\(_{H}\)1, T\(_{H}\)2, and T\(_{H}\)17 cells exhibited substantial variations between different individuals these ratios and the frequencies were relatively stable when tested in samples drawn up to five years apart. IFN-\({\gamma}\) and IL-2 co-expressing polyfunctional cells were seen in most subjects. Around half of the HCMV-specific CD4 cells were in a reversible state of exhaustion. The data provided here established the T\(_{H}\)1, T\(_{H}\)2, and T\(_{H}\)17 characteristic of the CD4 cells that convey immune protection for successful immune surveillance against which reactivity can be compared when the immune surveillance of HCMV fails.show moreshow less

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Metadaten
Author: Marie Wunsch, Wenji Zhang, Jodi Hanson, Richard Caspell, Alexey Y. Karulin, Mascha S. Recks, Stefanie Kuerten, Srividya Sundararaman, Paul V. Lehmann
URN:urn:nbn:de:bvb:20-opus-151462
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Anatomie und Zellbiologie
Language:English
Parent Title (English):Viruses
Year of Completion:2015
Volume:7
Source:Viruses 2015, 7, 4414-4437. DOI: 10.3390/v7082828
DOI:https://doi.org/10.3390/v7082828
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 616 Krankheiten
Tag:B cells; CD4 T cells; Enzyme-Linked Immunospot assay (ELISPOT); HCMV infection; activation; chronic viral infection; cytokine secretion kinetics; cytomegalovirus; elispot; exhaustion; hcv infection; human cytomegalovirus (HCMV); memory cells; signature
Release Date:2017/10/13
First Page:4414
Last Page:4437
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International