Next Article in Journal
RNA-Dependent RNA Polymerases of Picornaviruses: From the Structure to Regulatory Mechanisms
Previous Article in Journal
The Virus-Host Interplay: Biogenesis of +RNA Replication Complexes
Article Menu

Export Article

Open AccessArticle
Viruses 2015, 7(8), 4414-4437; doi:10.3390/v7082828

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

1
Department of Anatomy and Cell Biology, University of Wuerzburg, Koellikerstr 6, 97070 Wuerzburg, Germany
2
Cellular Technology Limited, 20521 Chagrin Blvd, Shaker Heights, OH 44022, USA
3
Department of Anatomy I, University of Cologne, Joseph-Stelzmann-Str. 9, 50931 Cologne, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Eric O. Freed
Received: 18 June 2015 / Revised: 15 July 2015 / Accepted: 27 July 2015 / Published: 6 August 2015
View Full-Text   |   Download PDF [3707 KB, uploaded 6 August 2015]   |  

Abstract

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 Immunospotr 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)- 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- 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. View Full-Text
Keywords: Human cytomegalovirus (HCMV); Enzyme-Linked Immunospot assay (ELISPOT); CD4 T cells; cytokine secretion; kinetics Human cytomegalovirus (HCMV); Enzyme-Linked Immunospot assay (ELISPOT); CD4 T cells; cytokine secretion; kinetics
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Wunsch, M.; Zhang, W.; Hanson, J.; Caspell, R.; Karulin, A.Y.; Recks, M.S.; Kuerten, S.; Sundararaman, S.; Lehmann, P.V. Characterization of the HCMV-Specific CD4 T Cell Responses that Are Associated with Protective Immunity. Viruses 2015, 7, 4414-4437.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Viruses EISSN 1999-4915 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top