Cytomegalovirus mediates expansion of IL-15-responsive innate-memory cells with SIV killing function.

Animals CD8-Positive T-Lymphocytes / immunology Cytomegalovirus / immunology Female Immunity, Innate Immunologic Memory Interleukin-15 / immunology Killer Cells, Natural / immunology Macaca mulatta Male Simian Acquired Immunodeficiency Syndrome / immunology Simian Immunodeficiency Virus / immunology
Cellular immune response Immunology Infectious disease Innate immunity T cells

Journal

The Journal of clinical investigation
ISSN: 1558-8238
Titre abrégé: J Clin Invest
Pays: United States
ID NLM: 7802877

Informations de publication

Date de publication:
02 08 2021
Historique:
received: 09 02 2021
accepted: 03 06 2021
pubmed: 22 6 2021
medline: 21 10 2021
entrez: 21 6 2021
Statut: ppublish

Résumé

Interindividual immune variability is driven predominantly by environmental factors, including exposure to chronic infectious agents such as cytomegalovirus (CMV). We investigated the effects of rhesus CMV (RhCMV) on composition and function of the immune system in young macaques. Within months of infection, RhCMV was associated with impressive changes in antigen presenting cells, T cells, and NK cells-and marked expansion of innate-memory CD8+ T cells. These cells express high levels of NKG2A/C and the IL-2 and IL-15 receptor beta chain, CD122. IL-15 was sufficient to drive differentiation of the cells in vitro and in vivo. Expanded NKG2A/C+CD122+CD8+ T cells in RhCMV-infected macaques, but not their NKG2-negative counterparts, were endowed with cytotoxicity against class I-deficient K562 targets and prompt IFN-γ production in response to stimulation with IL-12 and IL-18. Because RhCMV clone 68-1 forms the viral backbone of RhCMV-vectored SIV vaccines, we also investigated immune changes following administration of RhCMV 68-1-vectored SIV vaccines. These vaccines led to impressive expansion of NKG2A/C+CD8+ T cells with capacity to inhibit SIV replication ex vivo. Thus, CMV infection and CMV-vectored vaccination drive expansion of functional innate-like CD8 cells via host IL-15 production, suggesting that innate-memory expansion could be achieved by other vaccine platforms expressing IL-15.

Identifiants

DOI: 10.1172/JCI148542 PMID: 34153005 PMC: PMC8321572
pubmed: 34153005
pii: e148542
doi: 10.1172/JCI148542
pmc: PMC8321572
doi:
pii:

Substances chimiques

Interleukin-15 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI118451
Pays : United States
Organisme : NIH HHS
ID : P51 OD011107
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI150554
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI143554
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI027763
Pays : United States
Organisme : NIH HHS
ID : S10 OD010786
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI131568
Pays : United States

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Auteurs

Gema Méndez-Lagares (G)

California National Primate Research Center.
Department of Medical Microbiology and Immunology.

Ning Chin (N)

California National Primate Research Center.
Department of Medical Microbiology and Immunology.

W L William Chang (WLW)

California National Primate Research Center.
Department of Medical Microbiology and Immunology.

Jaewon Lee (J)

Graduate Group in Immunology, and.
Center for Immunology and Infectious Diseases, University of California Davis, Davis, California, USA.

Míriam Rosás-Umbert (M)

IrsiCaixa - AIDS Research Institute, Badalona, Barcelona, Spain.

Hung T Kieu (HT)

California National Primate Research Center.
Department of Medical Microbiology and Immunology.

David Merriam (D)

California National Primate Research Center.
Department of Medical Microbiology and Immunology.

Wenze Lu (W)

California National Primate Research Center.
Department of Medical Microbiology and Immunology.

Sungjin Kim (S)

Department of Medical Microbiology and Immunology.
Center for Immunology and Infectious Diseases, University of California Davis, Davis, California, USA.

Lourdes Adamson (L)

Center for Immunology and Infectious Diseases, University of California Davis, Davis, California, USA.

Christian Brander (C)

IrsiCaixa - AIDS Research Institute, Badalona, Barcelona, Spain.
Universitat de Vic-Universitat Central de Catalunya (UVic-UCC), Vic, Barcelona, Spain.
Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.

Paul A Luciw (PA)

California National Primate Research Center.
Center for Immunology and Infectious Diseases, University of California Davis, Davis, California, USA.
Department of Pathology and Laboratory Medicine, University of California, Davis, California, USA.

Peter A Barry (PA)

California National Primate Research Center.
Center for Immunology and Infectious Diseases, University of California Davis, Davis, California, USA.
Department of Pathology and Laboratory Medicine, University of California, Davis, California, USA.

Dennis J Hartigan-O'Connor (DJ)

California National Primate Research Center.
Department of Medical Microbiology and Immunology.
Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, California, USA.

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Classifications MeSH

Recherchemedicale.com › Eucaryotes › Animaux › Cytomegalovirus mediates expansion of...
Recherchemedicale.com › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Lymphocytes T CD8+ › Cytomegalovirus mediates expansion of...
Recherchemedicale.com › Virus › Virus à ADN › Herpesviridae › Betaherpesvirinae › Cytomegalovirus › Cytomegalovirus mediates expansion of...
Recherchemedicale.com › Phénomènes du système immunitaire › Immunité › Immunité innée › Cytomegalovirus mediates expansion of...
Recherchemedicale.com › Phénomènes du système immunitaire › Immunité › Immunité acquise › Mémoire immunologique › Cytomegalovirus mediates expansion of...
Recherchemedicale.com › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interleukines › Interleukine-15 › Cytomegalovirus mediates expansion of...
Recherchemedicale.com › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Cellules tueuses naturelles › Cytomegalovirus mediates expansion of...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Cercopithecidae › Cercopithecinae › Macaca › Macaca mulatta › Cytomegalovirus mediates expansion of...
Recherchemedicale.com › Maladies de l'animal › Maladies des primates › Maladies des singes › Syndrome d'immunodéficience acquise du singe › Cytomegalovirus mediates expansion of...
Recherchemedicale.com › Virus › Virus à ARN › Retroviridae › Rétrovirus simiens › Virus de l'immunodéficience simienne › Cytomegalovirus mediates expansion of...