Boosting vaccine efficacy the natural (killer) way

Rydyznski, Carolyn E.; Waggoner, Stephen N.

doi:10.1016/j.it.2015.07.004

Cited by 62 publications

(62 citation statements)

References 153 publications

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“…The immunologic environment at the time of CD4 + T‐cell priming thus has an important impact on initial Tfh induction, and regulatory cell populations including FoxP3 + CD4 + regulatory T cells (Tregs),215, 216 IL‐10‐producing regulatory B cells,217, 218 and natural killer (NK) cells219 may all modulate the generation of Tfh cells and hence influence GC formation and the subsequent humoral response.…”

Section: Regulatory Cell Populations and Their Relationship To Bnab Imentioning

confidence: 99%

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

Borrow

Moody

2017

Immunological Reviews

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SummaryInduction of broadly neutralizing antibodies (bnAbs) capable of inhibiting infection with diverse variants of human immunodeficiency virus type 1 (HIV‐1) is a key, as‐yet‐unachieved goal of prophylactic HIV‐1 vaccine strategies. However, some HIV‐infected individuals develop bnAbs after approximately 2‐4 years of infection, enabling analysis of features of these antibodies and the immunological environment that enables their induction. Distinct subsets of CD4+ T cells play opposing roles in the regulation of humoral responses: T follicular helper (Tfh) cells support germinal center formation and provide help for affinity maturation and the development of memory B cells and plasma cells, while regulatory CD4+ (Treg) cells including T follicular regulatory (Tfr) cells inhibit the germinal center reaction to limit autoantibody production. BnAbs exhibit high somatic mutation frequencies, long third heavy‐chain complementarity determining regions, and/or autoreactivity, suggesting that bnAb generation is likely to be highly dependent on the activity of CD4+ Tfh cells, and may be constrained by host tolerance controls. This review discusses what is known about the immunological environment during HIV‐1 infection, in particular alterations in CD4+ Tfh, Treg, and Tfr populations and autoantibody generation, and how this is related to bnAb development, and considers the implications for HIV‐1 vaccine design.

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Section: Regulatory Cell Populations and Their Relationship To Bnab Imentioning

confidence: 99%

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

Borrow

Moody

2017

Immunological Reviews

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“…Despite this, recent evidence in mice, humans and non-human primates confirms that NK cells can be long-lived and are capable of exerting antigen-specific immune responses against haptens and viruses (9–11). While NK cells have long been characterized as bridging the innate and adaptive immune systems, recent findings suggest that NK cells may develop antigen specific responses that can be manipulated through vaccination (9,12). …”

Section: Introductionmentioning

confidence: 99%

Phenotypic and Functional Characterization of Circulatory, Splenic, and Hepatic NK Cells in Simian Immunodeficiency Virus–Controlling Macaques

Vargas-Inchaustegui

Hait

Chung

et al. 2017

The Journal of Immunology

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NK cells are key components of the immune system due to their rapid response potential and their ability to mediate cytotoxic and immunomodulatory functions. Additionally, NK cells have recently been shown to persist for long periods in vivo and to have the capacity to establish immunologic memory. In the present study we studied the phenotype and function of circulatory and tissue-resident NK cells in a unique cohort of SIV controlling rhesus macaques that maintained low to undetectable levels of viremia in the chronic phase of infection. By contrasting NK responses of these macaques with those observed in SIV non-controlling and uninfected macaques we aimed to identify markers and activities of NK subpopulations associated with disease control. We show here that most differences among NK cells of the three groups of macaques were observed in tissue-resident cells. While SIV infection resulted in NK cell dysfunction, double negative NK cells, and those expressing CXCR3, NKG2D, and IL-18Rα were associated with viremia control, as was antibody-dependent cytotoxic function. Our results suggest several novel targets for therapeutic intervention.

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“…In addition to suppressing T cell expansion and cytokine production, some models have shown that suppressive NK cells/ILCs produce IL-10 (refs. 35,36), inhibit B cell function and memory 37,38 , and dampen immune responses by modulating DC function 39–41 , as well as limiting immunity by killing CD8 + T cells 19, 20 . While the majority of studies have described immunosuppressive ILCs as NK cells, the various shared and distinct properties of suppressive ILCs when compared to conventional NK cells and other ILC subsets are not well defined.…”

mentioning

confidence: 99%

A distinct innate lymphoid cell population regulates tumor-associated T cells

López‐Vergès

et al. 2017

Nat Med

134

107

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Antitumor T cells are subject to multiple mechanisms of negative regulation1–3. Recent findings that innate lymphoid cells (ILCs) regulate adaptive T cell responses4–6 led us to examine the regulatory potential of ILCs in the context of cancer. We identified a unique ILC population that inhibits tumor-infiltrating lymphocytes (TILs) from high-grade serous tumors, defined their suppressive capacity in vitro, and performed a comprehensive analysis of their phenotype. Notably, the presence of this CD56+CD3− population in TIL cultures was associated with reduced T cell numbers, and further functional studies demonstrated that this population suppressed TIL expansion and altered TIL cytokine production. Transcriptome analysis and phenotypic characterization determined that regulatory CD56+CD3− cells exhibit low cytotoxic activity, produce IL-22, and have an expression profile that overlaps with those of natural killer (NK) cells and other ILCs. NKp46 was highly expressed by these cells, and addition of anti-NKp46 antibodies to TIL cultures abrogated the ability of these regulatory ILCs to suppress T cell expansion. Notably, the presence of these regulatory ILCs in TIL cultures corresponded with a striking reduction in the time to disease recurrence. These studies demonstrate that a previously uncharacterized ILC population regulates the activity and expansion of tumor-associated T cells.

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Boosting vaccine efficacy the natural (killer) way

Cited by 62 publications

References 153 publications

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

Phenotypic and Functional Characterization of Circulatory, Splenic, and Hepatic NK Cells in Simian Immunodeficiency Virus–Controlling Macaques

A distinct innate lymphoid cell population regulates tumor-associated T cells

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