Characterization of the HCMV-Specific CD4 T Cell Responses that Are Associated with Protective Immunity
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 immun...
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| Format: | Online |
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MDPI
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4576189/ |
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pubmed-45761892015-09-28 Characterization of the HCMV-Specific CD4 T Cell Responses that Are Associated with Protective Immunity Wunsch, Marie Zhang, Wenji Hanson, Jodi Caspell, Richard Karulin, Alexey Y. Recks, Mascha S. Kuerten, Stefanie Sundararaman, Srividya Lehmann, Paul V. Article 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 TH1, TH2, and TH17 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)-γ 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 TH1, TH2, and TH17 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-γ 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 TH1, TH2, and TH17 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. MDPI 2015-08-06 /pmc/articles/PMC4576189/ /pubmed/26258786 http://dx.doi.org/10.3390/v7082828 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/). |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Wunsch, Marie Zhang, Wenji Hanson, Jodi Caspell, Richard Karulin, Alexey Y. Recks, Mascha S. Kuerten, Stefanie Sundararaman, Srividya Lehmann, Paul V. |
| spellingShingle |
Wunsch, Marie Zhang, Wenji Hanson, Jodi Caspell, Richard Karulin, Alexey Y. Recks, Mascha S. Kuerten, Stefanie Sundararaman, Srividya Lehmann, Paul V. Characterization of the HCMV-Specific CD4 T Cell Responses that Are Associated with Protective Immunity |
| author_facet |
Wunsch, Marie Zhang, Wenji Hanson, Jodi Caspell, Richard Karulin, Alexey Y. Recks, Mascha S. Kuerten, Stefanie Sundararaman, Srividya Lehmann, Paul V. |
| author_sort |
Wunsch, Marie |
| title |
Characterization of the HCMV-Specific CD4 T Cell Responses that Are Associated with Protective Immunity |
| title_short |
Characterization of the HCMV-Specific CD4 T Cell Responses that Are Associated with Protective Immunity |
| title_full |
Characterization of the HCMV-Specific CD4 T Cell Responses that Are Associated with Protective Immunity |
| title_fullStr |
Characterization of the HCMV-Specific CD4 T Cell Responses that Are Associated with Protective Immunity |
| title_full_unstemmed |
Characterization of the HCMV-Specific CD4 T Cell Responses that Are Associated with Protective Immunity |
| title_sort |
characterization of the hcmv-specific cd4 t cell responses that are associated with protective immunity |
| description |
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 TH1, TH2, and TH17 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)-γ 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 TH1, TH2, and TH17 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-γ 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 TH1, TH2, and TH17 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. |
| publisher |
MDPI |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4576189/ |
| _version_ |
1613477585679810560 |