α-Galactosylceramide Can Act As a Nasal Vaccine Adjuvant Inducing Protective Immune Responses against Viral Infection and Tumor

Ko, Seungbeom; Ko, Hyun Jeong; Chang, Woo Sung; Park, Seho; Kweon, Mi Na; Kang, Chung Nam

doi:10.4049/jimmunol.175.5.3309

Cited by 165 publications

(141 citation statements)

References 43 publications

Supporting

Mentioning

127

Contrasting

Unclassified

Order By: Relevance

“…In murine models, CD1d and iNKT cells are required for the generation of protective antibody responses against microbial pathogens [167][168][169]. Coadministration of a-GC with immunizing antigen to mice results in enhanced production of antibodies specific for the antigen [170][171][172], demonstrating that the adjuvant effect of iNKT cells is antigen-specific. This help provided by iNKT cells results in the induction of long-lived antibody-secreting plasma cells, affinity maturation and the generation of memory B cells [172][173][174][175].…”

Section: Other Unconventional T Cells Bridging Innate and Adaptive Immentioning

confidence: 99%

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Tyler

Doherty

Moser

et al. 2015

Cellular Immunology

View full text Add to dashboard Cite

a b s t r a c tUnconventional T cells are gaining center stage as important effector and regulatory cells that orchestrate innate and adaptive immune responses. Human Vc9/Vd2 T cells are amongst the best understood unconventional T cells, as they are easily accessible in peripheral blood, can readily be expanded and manipulated in vitro, respond to microbial infections in vivo and can be exploited for novel tumor immunotherapies. We here review findings that suggest that Vc9/Vd2 T cells, and possibly other unconventional human T cells, play an important role in bridging innate and adaptive immunity by promoting the activation and differentiation of various types of antigen-presenting cells (APCs) and even turning into APCs themselves, and thereby pave the way for antigen-specific effector responses and long-term immunological memory. Although the direct physiological relevance for most of these mechanisms still needs to be demonstrated in vivo, these findings may have implications for novel therapies, diagnostic tests and vaccines.Ó 2015 Published by Elsevier Inc. Introduction cd T cells represent a third lineage of lymphocytes expressingre-arranged antigen receptors that co-evolved with 'classical' B cells and ab T cells over 400 million years, arguing for a crucial and non-redundant contribution of each lymphocyte to effective immune responses, and hence the evolutionary survival of all jawed vertebrate species [1]. 30 years have passed since the accidental and unexpected cloning of the cd T cell receptor (TCR) and the subsequent realization that ab T cells and cd T cells are fundamentally different with respect to the types of antigens they recognize and the distinct effector functions triggered upon such recognition. However, the manifold contributions of cd T cells to homeostasis, inflammation, infection and tumor surveillance have historically been neglected and are only beginning to be integrated into comprehensive models of the immune system [1][2][3][4][5][6][7].1. Innate-like pattern recognition by human Vc9/Vd2 T cells Like other 'unconventional' T cells carrying an ab TCR such as mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells, cd T cells are characterized by a markedly restrictedTCR usage that allows them to recognize self and non-self molecules in the absence of classical antigen presentation via MHC I or MHC II. Vc9/Vd2 + cd T cells represent the major cd T cell subset in human peripheral blood where they typically comprise 1-5% in healthy adults [8]. In many microbial infections, Vc9/Vd2 T cells increase locally and/or systemically [9,10] and can reach in excess of 50% of all peripheral T cells within a matter of days [11], revealing a fundamental role of this unconventional T cell population in acute disease and suggesting their exploitation for diagnostic and therapeutic purposes [12][13][14]. Vc9/Vd2 T cells uniformly respond to a class of low molecular weight molecules often referred to as 'phosphoantigens' that represent metabolites of the isoprenoid biosynthesis...

show abstract

Section: Other Unconventional T Cells Bridging Innate and Adaptive Immentioning

confidence: 99%

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Tyler

Doherty

Moser

et al. 2015

Cellular Immunology

View full text Add to dashboard Cite

show abstract

“…Stimulation by both IL-4 and IL-13 was also required for iNKT-cell-derived B-cell help, whereas CD40L-CD40 interactions were only partially involved in these responses [32]. Accordingly, the T H 0 CD4 + iNKT-cell subset was markedly more efficient than the T H 1 CD4 − iNKT-cell subset in providing B-cell help [32].Subsequent studies demonstrated that immunization of mice with αGalCer along with protein or hapten-carrier Ags elicits high titers of Ag-specific, class-switched Abs [33][34][35], significantly enhancing features of the Ab response in vivo, such as protection from infections [33,35] and long-lasting B-cell memory [35]. The adjuvant effect of αGalCer was comparable to that of benchmark adjuvants that are being utilized for human vaccination [35] and was independent of the route of administration [35].…”

mentioning

confidence: 99%

iNKT‐cell help to B cells: A cooperative job between innate and adaptive immune responses

2014

View full text Add to dashboard Cite

T-cell help to B lymphocytes is one of the most important events in adaptive immune responses in health and disease. It is generally delivered by cognate CD4 + T follicular helper (T FH ) cells via both cell-to-cell contacts and soluble mediators, and it is essential for both the clonal expansion of antibody (Ab)-secreting B cells and memory B-cell formation. CD1d-restricted invariant natural killer T (iNKT) cells are a subset of innate-like T lymphocytes that rapidly respond to stimulation with specific lipid antigens (Ags) that are derived from infectious pathogens or stressed host cells. Activated iNKT cells produce a wide range of cytokines and upregulate costimulatory molecules that can promote activation of dendritic cells (DCs), natural killer (NK) cells, and T cells. A decade ago, we discovered that iNKT cells can help B cells to proliferate and to produce IgG Abs in vitro and in vivo. This adjuvant-like function of Ag-activated iNKT cells provides a flexible set of helper mechanisms that expand the current paradigm of T-cell-B-cell interaction and highlights the potential of iNKT-cell targeting vaccine formulations.Keywords: B-cell help r CD1d r T follicular helper cells r vaccines IntroductionThe production of neutralizing antibodies (Abs) by B cells represents a major parameter of host defense against infectious pathogens and is a key component of protective immune responses elicited by vaccines [1]. The innate and adaptive arms of the immune system are functionally separated, but seem to be highly coordinated to ensure an optimal outcome of immune responses. Although innate and adaptive immune cells are endowed with very distinct functions and timing of response, there are specialized lymphocyte subsets that straddle the two programs, and these cells have been defined as innate-like lymphocytes [2]. CD1d-rectricted invariant Vα14 natural killer T (iNKT) cells are one of the best characterized types of innate-like T lymphocytes, which display multiple effector functions upon activation [3]. Here, we review the mechanisms through which iNKT cells help B cells to promote Ab production and memory formation.Correspondence: Dr. Paolo Dellabona e-mail: dellabona.paolo@hsr.itThe TD and TI paradigm of the B-cell response B-cell responses are generally described as T-dependent (TD) or T-independent (TI), based on the requirement for T-cell help for Ab production. TD responses are induced by protein antigens (Ags) that are recognized by specific B cells in the presence of cognate T-cell help, which is provided by a specialized subset of CD4 + T helper (Th) cells called T follicular helper (T FH ) cells [4]. Ags reach the follicles, the B-cell zone of secondary lymphoid organs, and activate B cells upon binding to the specific B-cell receptors (BCRs [5]). This leads to Ag internalization, presentation of the processed Ag peptides into MHC class II (MHC II) molecules, and migration of the activated B cells to the border of the T-B-cell zone [4]. T FH cells are induced in the T-cell zone by dendritic cells (DCs) t...

show abstract

mentioning

confidence: 99%

“…Such experiments have shown that combining iIAV vaccine with ␣-GalCer can significantly enhance protective efficacy (15)(16)(17)(18). However, though CTL cytotoxicity could be demonstrated after in vitro restimulation, no attempt was made to enumerate IAV-specific CD8 ϩ T cell numbers directly ex vivo (16). Furthermore, as these studies used homologous virus challenge, preexisting neutralizing antibody rather than the recall of virus-specific CTL memory was the likely mechanism of immune protection (16,17).…”

mentioning

confidence: 99%

“…However, though CTL cytotoxicity could be demonstrated after in vitro restimulation, no attempt was made to enumerate IAV-specific CD8 ϩ T cell numbers directly ex vivo (16). Furthermore, as these studies used homologous virus challenge, preexisting neutralizing antibody rather than the recall of virus-specific CTL memory was the likely mechanism of immune protection (16,17). Thus, though NKT cell activation appears to enhance immunity to influenza, the question remains: do ␣-GalCer-adjuvanted influenza vaccines augment heterologous CTL-mediated immunity?…”

mentioning

confidence: 99%

See 1 more Smart Citation

Combined NKT cell activation and influenza virus vaccination boosts memory CTL generation and protective immunity

Guillonneau

Mintern

Hubert

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

118

View full text Add to dashboard Cite

Current influenza A virus vaccines do not generate significant immunity against serologically distinct influenza A virus subtypes and would thus be ineffective in the face of a pandemic caused by a novel variant emerging from, say, a wildlife reservoir. One possible solution would be to modify these vaccines so that they prime cross-reactive CD8 ؉ cytotoxic T lymphocytes (CTL) cellmediated immunity directed at conserved viral epitopes. A further strategy is to use novel adjuvants, such as the immunomodulatory glycolipid ␣-galactosylceramide (␣-GalCer). We show here that giving ␣-GalCer with an inactivated influenza A virus has the paradoxical effect of diminishing acute CTL immunity via natural killer T (NKT) cell-dependent expression of indoleamine 2,3-dioxygenase (IDO), an important mediator of immune suppression, while at the same time promoting the survival of long-lived memory CTL populations capable of boosting protection against heterologous influenza A virus challenge. This enhancement of memory was likely due to the ␣-GalCer-induced upregulation of prosurvival genes, such as bcl-2, and points to the potential of ␣-GalCer as an adjuvant for promoting optimal, vaccine-induced CD8 ؉ T cell memory.T cell memory ͉ viral immunity ͉ vaccine ͉ adjuvant

show abstract

α-Galactosylceramide Can Act As a Nasal Vaccine Adjuvant Inducing Protective Immune Responses against Viral Infection and Tumor

Cited by 165 publications

References 43 publications

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

iNKT‐cell help to B cells: A cooperative job between innate and adaptive immune responses

Combined NKT cell activation and influenza virus vaccination boosts memory CTL generation and protective immunity

Contact Info

Product

Resources

About