Generation of Cellular Immune Memory and B-cell Immunity is Impaired by Natural Killer Cells

Overview

Journal Nat Commun

Specialty Biology

Date 2015 Feb 28

PMID 25721802

Citations 80

Authors

Carolyn Rydyznski

Keith A Daniels

Erik P Karmele

Taylor R Brooks

Sarah E Mahl

Michael T Moran

Caimei Li

Rujapak Sutiwisesak

Raymond M Welsh

Stephen N Waggoner

Affiliations

Soon will be listed here.

Abstract

The goal of most vaccines is the induction of long-lived memory T and B cells capable of protecting the host from infection by cytotoxic mechanisms, cytokines and high-affinity antibodies. However, efforts to develop vaccines against major human pathogens such as HIV and HCV have not been successful, thereby highlighting the need for novel approaches to circumvent immunoregulatory mechanisms that limit the induction of protective immunity. Here, we show that mouse natural killer (NK) cells inhibit generation of long-lived virus-specific memory T- and B cells as well as virus-specific antibody production after acute infection. Mechanistically, NK cells suppressed CD4 T cells and follicular helper T cells (T(FH)) in a perforin-dependent manner during the first few days of infection, resulting in a weaker germinal centre (GC) response and diminished immune memory. We anticipate that innovative strategies to relieve NK cell-mediated suppression of immunity should facilitate development of efficacious new vaccines targeting difficult-to-prevent infections.

Citing Articles

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KLF2 determines the susceptibility of T cells to immunoregulatory NK cells.

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References

Kagi D, Ledermann B, Burki K, Seiler P, Odermatt B, Olsen K . Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice. Nature. 1994; 369(6475):31-7. DOI: 10.1038/369031a0. View

Selin L, Nahill S, Welsh R . Cross-reactivities in memory cytotoxic T lymphocyte recognition of heterologous viruses. J Exp Med. 1994; 179(6):1933-43. PMC: 2191532. DOI: 10.1084/jem.179.6.1933. View

Maggi E, Giudizi M, Biagiotti R, Annunziato F, Manetti R, Piccinni M . Th2-like CD8+ T cells showing B cell helper function and reduced cytolytic activity in human immunodeficiency virus type 1 infection. J Exp Med. 1994; 180(2):489-95. PMC: 2191625. DOI: 10.1084/jem.180.2.489. View

Wilder J, Koh C, Yuan D . The role of NK cells during in vivo antigen-specific antibody responses. J Immunol. 1996; 156(1):146-52. View

Mendiratta S, Martin W, Hong S, Boesteanu A, Joyce S, Van Kaer L . CD1d1 mutant mice are deficient in natural T cells that promptly produce IL-4. Immunity. 1997; 6(4):469-77. DOI: 10.1016/s1074-7613(00)80290-3. View

Crotty S . Follicular helper CD4 T cells (TFH). Annu Rev Immunol. 2011; 29:621-63. DOI: 10.1146/annurev-immunol-031210-101400. View

Stadnisky M, Xie X, Coats E, Bullock T, Brown M . Self MHC class I-licensed NK cells enhance adaptive CD8 T-cell viral immunity. Blood. 2011; 117(19):5133-41. PMC: 3109538. DOI: 10.1182/blood-2010-12-324632. View

Waggoner S, Cornberg M, Selin L, Welsh R . Natural killer cells act as rheostats modulating antiviral T cells. Nature. 2011; 481(7381):394-8. PMC: 3539796. DOI: 10.1038/nature10624. View

Mitrovic M, Arapovic J, Jordan S, Fodil-Cornu N, Ebert S, Vidal S . The NK cell response to mouse cytomegalovirus infection affects the level and kinetics of the early CD8(+) T-cell response. J Virol. 2011; 86(4):2165-75. PMC: 3302391. DOI: 10.1128/JVI.06042-11. View

10.

Lang P, Lang K, Xu H, Grusdat M, Parish I, Recher M . Natural killer cell activation enhances immune pathology and promotes chronic infection by limiting CD8+ T-cell immunity. Proc Natl Acad Sci U S A. 2011; 109(4):1210-5. PMC: 3268324. DOI: 10.1073/pnas.1118834109. View

11.

Victora G, Nussenzweig M . Germinal centers. Annu Rev Immunol. 2012; 30:429-57. DOI: 10.1146/annurev-immunol-020711-075032. View

12.

Kwong P, Mascola J, Nabel G . The changing face of HIV vaccine research. J Int AIDS Soc. 2012; 15(2):17407. PMC: 3499796. DOI: 10.7448/IAS.15.2.17407. View

13.

Rowe J, Ertelt J, Xin L, Way S . Listeria monocytogenes cytoplasmic entry induces fetal wastage by disrupting maternal Foxp3+ regulatory T cell-sustained fetal tolerance. PLoS Pathog. 2012; 8(8):e1002873. PMC: 3420962. DOI: 10.1371/journal.ppat.1002873. View

14.

Welsh R, Waggoner S . NK cells controlling virus-specific T cells: Rheostats for acute vs. persistent infections. Virology. 2012; 435(1):37-45. PMC: 3521501. DOI: 10.1016/j.virol.2012.10.005. View

15.

Cook K, Whitmire J . The depletion of NK cells prevents T cell exhaustion to efficiently control disseminating virus infection. J Immunol. 2012; 190(2):641-9. PMC: 3879798. DOI: 10.4049/jimmunol.1202448. View

16.

Dong C, Juedes A, Temann U, Shresta S, Allison J, Ruddle N . ICOS co-stimulatory receptor is essential for T-cell activation and function. Nature. 2001; 409(6816):97-101. DOI: 10.1038/35051100. View

17.

McAdam A, Greenwald R, Levin M, Chernova T, Malenkovich N, Ling V . ICOS is critical for CD40-mediated antibody class switching. Nature. 2001; 409(6816):102-5. DOI: 10.1038/35051107. View

18.

Kelly J, Darcy P, Markby J, Godfrey D, Takeda K, Yagita H . Induction of tumor-specific T cell memory by NK cell-mediated tumor rejection. Nat Immunol. 2001; 3(1):83-90. DOI: 10.1038/ni746. View

19.

Brehm M, Pinto A, Daniels K, Schneck J, Welsh R, Selin L . T cell immunodominance and maintenance of memory regulated by unexpectedly cross-reactive pathogens. Nat Immunol. 2002; 3(7):627-34. DOI: 10.1038/ni806. View

20.

Huber S, Sartini D, Exley M . Role of CD1d in coxsackievirus B3-induced myocarditis. J Immunol. 2003; 170(6):3147-53. DOI: 10.4049/jimmunol.170.6.3147. View