Evolution of T Cell Responses during Measles Virus Infection and RNA Clearance

Ashley N Nelson; Nicole Putnam; Debra Hauer; Victoria K Baxter; Robert J Adams; Diane E Griffin

doi:10.1038/s41598-017-10965-z

Evolution of T Cell Responses during Measles Virus Infection and RNA Clearance

Sci Rep. 2017 Sep 13;7(1):11474. doi: 10.1038/s41598-017-10965-z.

Authors

Ashley N Nelson¹, Nicole Putnam^{1

2}, Debra Hauer¹, Victoria K Baxter^{1

3

4}, Robert J Adams³, Diane E Griffin⁵

Affiliations

¹ W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
² Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
³ Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
⁴ University of North Carolina School of Medicine, Chapel Hill, NC, USA.
⁵ W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. dgriffi6@jhu.edu.

Abstract

Measles is an acute viral disease associated both with immune suppression and development of life-long immunity. Clearance of measles virus (MeV) involves rapid elimination of infectious virus during the rash followed by slow elimination of viral RNA. To characterize cellular immune responses during recovery, we analyzed the appearance, specificity and function of MeV-specific T cells for 6 months after respiratory infection of rhesus macaques with wild type MeV. IFN-γ and IL-17-producing cells specific for the hemagglutinin and nucleocapsid proteins appeared in circulation in multiple waves approximately 2-3, 8 and 18-24 weeks after infection. IFN-γ-secreting cells were most abundant early and IL-17-secreting cells late. Both CD4⁺ and CD8⁺ T cells were sources of IFN-γ and IL-17, and IL-17-producing cells expressed RORγt. Therefore, the cellular immune response evolves during MeV clearance to produce functionally distinct subsets of MeV-specific CD4⁺ and CD8⁺ T cells at different times after infection.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biological Evolution
CD4-Positive T-Lymphocytes / immunology
CD4-Positive T-Lymphocytes / metabolism
CD8-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / metabolism
Cell Line
Cytokines
Gene Expression
Host-Pathogen Interactions / immunology*
Leukocyte Count
Macaca mulatta
Male
Measles / immunology*
Measles / virology*
Measles virus / immunology*
Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
RNA, Viral
T-Cell Antigen Receptor Specificity / genetics
T-Cell Antigen Receptor Specificity / immunology
T-Lymphocytes / immunology*
T-Lymphocytes / metabolism
Viral Load
Viremia
Virus Shedding

Substances

Cytokines
Nuclear Receptor Subfamily 1, Group F, Member 3
RNA, Viral

Abstract

Publication types

MeSH terms

Substances

Grants and funding