Tissue reservoirs of antiviral T cell immunity in persistent human CMV infection

Claire L. Gordon, Michelle Miron, Joseph J.C. Thome, Nobuhide Matsuoka, Joshua Weiner, Michael A. Rak, Suzu Igarashi, Tomer Granot, Harvey Lerner, Felicia Goodrum, Donna L. Farber

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

T cell responses to viruses are initiated and maintained in tissue sites; however, knowledge of human antiviral T cells is largely derived from blood. Cytomegalovirus (CMV) persists in most humans, requires T cell immunity to control, yet tissue immune responses remain undefined. Here, we investigated human CMV-specific T cells, virus persistence and CMV-associated T cell homeostasis in blood, lymphoid, mucosal and secretory tissues of 44 CMV seropositive and 28 seronegative donors. CMVspecific T cells were maintained in distinct distribution patterns, highest in blood, bone marrow (BM), or lymph nodes (LN), with the frequency and function in blood distinct from tissues. CMV genomes were detected predominantly in lung and also in spleen, BM, blood and LN. High frequencies of activated CMV-specific T cells were found in blood and BM samples with low virus detection, whereas in lung, CMV-specific T cells were present along with detectable virus. In LNs, CMV-specific T cells exhibited quiescent phenotypes independent of virus. Overall, T cell differentiation was enhanced in sites of viral persistence with age. Together, our results suggest tissue T cell reservoirs for CMV control shaped by both viral and tissue-intrinsic factors, with global effects on homeostasis of tissue T cells over the lifespan.

Original languageEnglish (US)
Pages (from-to)651-667
Number of pages17
JournalJournal of Experimental Medicine
Volume214
Issue number3
DOIs
StatePublished - Jan 27 2017

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Cytomegalovirus Infections
Antiviral Agents
Immunity
Cytomegalovirus
T-Lymphocytes
Viruses
Bone Marrow
Homeostasis
Lymph Nodes
Lung
Intrinsic Factor
Thromboplastin
Cell Differentiation
Mucous Membrane
Spleen
Genome
Phenotype

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Gordon, C. L., Miron, M., Thome, J. J. C., Matsuoka, N., Weiner, J., Rak, M. A., ... Farber, D. L. (2017). Tissue reservoirs of antiviral T cell immunity in persistent human CMV infection. Journal of Experimental Medicine, 214(3), 651-667. https://doi.org/10.1084/jem.20160758

Tissue reservoirs of antiviral T cell immunity in persistent human CMV infection. / Gordon, Claire L.; Miron, Michelle; Thome, Joseph J.C.; Matsuoka, Nobuhide; Weiner, Joshua; Rak, Michael A.; Igarashi, Suzu; Granot, Tomer; Lerner, Harvey; Goodrum, Felicia; Farber, Donna L.

In: Journal of Experimental Medicine, Vol. 214, No. 3, 27.01.2017, p. 651-667.

Research output: Contribution to journalArticle

Gordon, CL, Miron, M, Thome, JJC, Matsuoka, N, Weiner, J, Rak, MA, Igarashi, S, Granot, T, Lerner, H, Goodrum, F & Farber, DL 2017, 'Tissue reservoirs of antiviral T cell immunity in persistent human CMV infection', Journal of Experimental Medicine, vol. 214, no. 3, pp. 651-667. https://doi.org/10.1084/jem.20160758
Gordon CL, Miron M, Thome JJC, Matsuoka N, Weiner J, Rak MA et al. Tissue reservoirs of antiviral T cell immunity in persistent human CMV infection. Journal of Experimental Medicine. 2017 Jan 27;214(3):651-667. https://doi.org/10.1084/jem.20160758
Gordon, Claire L. ; Miron, Michelle ; Thome, Joseph J.C. ; Matsuoka, Nobuhide ; Weiner, Joshua ; Rak, Michael A. ; Igarashi, Suzu ; Granot, Tomer ; Lerner, Harvey ; Goodrum, Felicia ; Farber, Donna L. / Tissue reservoirs of antiviral T cell immunity in persistent human CMV infection. In: Journal of Experimental Medicine. 2017 ; Vol. 214, No. 3. pp. 651-667.
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