B Cell Help by CD1d-Rectricted NKT Cells

Clerici, Livia; Casorati, Giulia; Dellabona, Paolo

doi:10.3390/antib4040279

Cited by 7 publications

(9 citation statements)

References 83 publications

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“…iNKT cells are a subset of innate-like T cells that expresses semiinvariant TCR (12,13) and recognizes lipid Ags presented by CD1d molecules (14). It has been reported that iNKT cells could provide help to B cells directly or indirectly (15,16). During indirect help, iNKT cells promote the maturation of dendritic cells (DCs) through cognate interactions, and educated DCs enhance the development of T FH cells (17,18).…”

mentioning

confidence: 99%

Memory Follicular Helper Invariant NKT Cells Recognize Lipid Antigens on Memory B Cells and Elicit Antibody Recall Responses

Chen

Zhu

Wang

et al. 2018

The Journal of Immunology

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Invariant NKT (iNKT) cells have been shown to help B cells in a cognate or noncognate manner; however, whether cognate iNKT cell help induces B cell memory responses remains controversial, and the underlying mechanisms are still unclear. In this study, we demonstrated that, in the absence of follicular helper T cells, cognate iNKT cell help could promote B cell memory responses in mice that were dependent on the formation of memory follicular helper iNKT (iNKT) cells and their interactions with memory B cells in recall responses. Generation of memory iNKT cells required lipid Ag presentation by dendritic cells but not by B cells. Upon rechallenge, memory iNKT cells recognized lipid Ags presented by memory B cells, which recalled iNKT effector cells and elicited B cell memory responses. However, LPS, which promoted the synthesis of self-lipids, failed to elicit recall responses in the absence of exogenous lipid Ags.

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mentioning

confidence: 99%

Memory Follicular Helper Invariant NKT Cells Recognize Lipid Antigens on Memory B Cells and Elicit Antibody Recall Responses

Chen

Zhu

Wang

et al. 2018

The Journal of Immunology

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“…In order to produce IgG antibodies, B cells require the cooperation of a T cell subset that expresses CD40L and produces class-switching cytokines, such as IL-4 or IFN-γ. NKT cells are lymphocytes restricted to the recognition of lipid antigens presented by CD1d molecules [ 20 ], and could provide the cooperation required to produce the IgG anti-NPA antibodies detected in C57BL/6 mice that received NPA-bearing liposomes. Here we evaluated the number of NK1.1 + , CD4 + T cells and their activation in C57BL/6 mice that produce anti-NPA antibodies.…”

Section: Resultsmentioning

confidence: 99%

“…NKT cells respond rapidly to antigenic stimulation by secreting IL-4 and IFN-γ, which results in the activation of numerous immune cells, including dendritic cells, NK cells, B cells and CD4 + and CD8 + T cells [24]. NKT cells interact through their TCR with CD1dexpressing B cells, and this interaction leads to B cell proliferation and antibody production, and to increased NKT cell activation [20,21,25]. This cooperation requires the expression of CD40 on B cells and of CD40L on NKT cells; likewise, it needs the production of IL-4 and antibodies against lipid antigens [20].…”

Section: Introductionmentioning

confidence: 99%

“…However, classical MHC molecules do not present lipid antigens. NKT cells are lymphocytes restricted to the recognition of lipid antigens presented by CD1d molecules, an antigen-presenting molecule similar to MHC class I molecules, on B cells or dendritic cells [ 20 ], with both innate and adaptive functions [ 20 , 21 ]. Human and murine NKT cells are a distinct subset of T cells that express both a T cell receptor (TCR α/β and CD3) and NK cell lineage markers [NK1.1 (CD161), CD122 (IL-2Rβ) and various Ly49 molecules] [ 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

“…NKT cells respond rapidly to antigenic stimulation by secreting IL-4 and IFN-γ, which results in the activation of numerous immune cells, including dendritic cells, NK cells, B cells and CD4 + and CD8 + T cells [ 24 ]. NKT cells interact through their TCR with CD1d-expressing B cells, and this interaction leads to B cell proliferation and antibody production, and to increased NKT cell activation [ 20 , 21 , 25 ]. This cooperation requires the expression of CD40 on B cells and of CD40L on NKT cells; likewise, it needs the production of IL-4 and IFN-γ by activated NKT cells, two essential cytokines that induce the class-switching of antibodies against lipid antigens [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Liposomes Bearing Non-Bilayer Phospholipid Arrangements Induce Specific IgG Anti-Lipid Antibodies by Activating NK1.1+, CD4+ T Cells in Mice

et al. 2022

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Liposomes are artificial models of cellular membranes that are used as delivery systems for genes, drugs and protein antigens. We have previously used them to study the antigenic properties of their phospholipids. Here, we used them to induce the production of IgG anti-non-bilayer phospholipid arrangements (NPAs) antibodies in mice; these antibodies cause cell lysis and trigger a lupus-like disease in mice. We studied the mechanisms that lead to the production of these antibodies, and provide evidence that NK1.1+, CD4+ T cells respond to NPA-bearing liposomes and deliver the help required for specific B cell activation and antibody class-switching to IgG. We found increased numbers of IL-4-producing NK1.1+, CD4+ T cells in the secondary lymphoid organs of mice administered with NPAs, and these cells also expressed CD40L, which is required for B cell activation. Additionally, we isolated and purified NK1.1+, CD4+ T cells from spleens and determined that they over-expressed 40 genes, which are key players in inflammatory processes and B cell stimulation and have TRAF6 and UNC39B1 as key nodes in their network. These results show that liposomes are membrane models that can be used to analyze the immunogenicity of lipids.

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Vaccination with mycobacterial lipid loaded nanoparticle leads to lipid antigen persistence and memory differentiation of antigen-specific T cells

Morgun

Zhu

Almunif

et al. 2023

Preprint

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Mycobacterium tuberculosis(Mtb) infection elicits both protein and lipid antigen-specific T cell responses. However, the incorporation of lipid antigens into subunit vaccine strategies and formulations has been under-explored, and the properties of vaccine-induced Mtb lipid-specific memory T cells have remained elusive. Mycolic acid (MA), a major lipid component of the Mtb cell wall, is presented by human CD1b molecules to unconventional T cell subsets. These MA-specific CD1b-restricted T cells have been detected in the blood and disease sites of Mtb-infected individuals, suggesting that MA is a promising lipid antigen for incorporation into multicomponent subunit vaccines. In this study, we utilized the enhanced stability of bicontinuous nanospheres (BCN) to efficiently encapsulate MA for deliveryin vivoto MA-specific T cells both alone and in combination with an immunodominant Mtb protein antigen (Ag85B). Pulmonary delivery of MA-loaded BCN (MA-BCN) elicited MA-specific T cell responses in humanized CD1 transgenic mice. Simultaneous delivery of MA and Ag85B within BCN activated both MA- and Ag85B-specific T cells. Interestingly, pulmonary vaccination with MA-Ag85B-BCN led to the persistence of MA, but not Ag85B, within alveolar macrophages in the lung. Vaccination of MA-BCN through intravenous or subcutaneous route, or with attenuated Mtb likewise reproduced MA persistence. Moreover, MA-specific T cells in MA-BCN-vaccinated mice differentiated into a T follicular helper-like phenotype. Overall, the BCN platform allows for the dual encapsulation andin vivoactivation of lipid and protein antigen-specific T cells and leads to persistent lipid depots that could offer long-lasting immune responses.

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B Cell Help by CD1d-Rectricted NKT Cells

Cited by 7 publications

References 83 publications

Memory Follicular Helper Invariant NKT Cells Recognize Lipid Antigens on Memory B Cells and Elicit Antibody Recall Responses

Memory Follicular Helper Invariant NKT Cells Recognize Lipid Antigens on Memory B Cells and Elicit Antibody Recall Responses

Liposomes Bearing Non-Bilayer Phospholipid Arrangements Induce Specific IgG Anti-Lipid Antibodies by Activating NK1.1+, CD4+ T Cells in Mice

Vaccination with mycobacterial lipid loaded nanoparticle leads to lipid antigen persistence and memory differentiation of antigen-specific T cells

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